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  <import namespace="http://www.xbrl.org/2009/role/negated" schemaLocation="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd" />
  <import namespace="http://fasb.org/us-gaap/2019-01-31" schemaLocation="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd" />
  <import namespace="http://fasb.org/srt/2019-01-31" schemaLocation="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd" />
  <element name="AdditionalSharesReservedSharesAvailableForGrant" id="pacb_AdditionalSharesReservedSharesAvailableForGrant" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" />
  <element name="AtTheMarketOfferingMember" id="pacb_AtTheMarketOfferingMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" />
  <element id="pacb_AvailableForSaleSecuritiesGrossUnrealizedGainAccumulatedInInvestments" name="AvailableForSaleSecuritiesGrossUnrealizedGainAccumulatedInInvestments" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="credit" />
  <element id="pacb_AvailableForSaleSecuritiesGrossUnrealizedLossAccumulatedInInvestments" name="AvailableForSaleSecuritiesGrossUnrealizedLossAccumulatedInInvestments" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <element name="CarryingValuesAndEstimatedFairValuesOfDebtTableTextBlock" id="pacb_CarryingValuesAndEstimatedFairValuesOfDebtTableTextBlock" type="nonnum:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" />
  <element name="CashAndCashEquivalentBalanceToBeMaintainedQuarterlyUnderFacilityAgreementMinimum" id="pacb_CashAndCashEquivalentBalanceToBeMaintainedQuarterlyUnderFacilityAgreementMinimum" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" />
  <element name="CashAndMoneyMarketFundsMember" id="pacb_CashAndMoneyMarketFundsMember" type="nonnum:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" />
  <element name="FairValueAssetsLiabilitiesTransferBetweenLevels" id="pacb_FairValueAssetsLiabilitiesTransferBetweenLevels" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" />
  <element id="pacb_OfferingShareAmountMaximum" name="OfferingShareAmountMaximum" nillable="true" type="num:perShareItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" />
  <element name="PercentageOfNetProceedsToBeAppliedFromFinancing" id="pacb_PercentageOfNetProceedsToBeAppliedFromFinancing" type="num:percentItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" />
  <element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantExercisedInPeriod" id="pacb_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantExercisedInPeriod" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" />
  <element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantForfeituresInPeriod" id="pacb_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantForfeituresInPeriod" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" />
  <element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantGrantsInPeriod" id="pacb_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrantGrantsInPeriod" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" />
  <element name="ShareBasedCompensationArrangementsByShareBasedPaymentAwardsNumberOfActivePlans" id="pacb_ShareBasedCompensationArrangementsByShareBasedPaymentAwardsNumberOfActivePlans" type="xbrli:integerItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" />
  <element name="WeightedAverageMarketYieldPercentage" id="pacb_WeightedAverageMarketYieldPercentage" type="num:percentItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" />
  <element id="pacb_EntityWideNetAccountsReceivableNumberOfMajorCustomer" name="EntityWideNetAccountsReceivableNumberOfMajorCustomer" nillable="true" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" />
  <element id="pacb_ExercisePriceRangeOneMember" name="ExercisePriceRangeOneMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <element id="pacb_ExercisePriceRangeTwoMember" name="ExercisePriceRangeTwoMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <element id="pacb_ExercisePriceRangeThreeMember" name="ExercisePriceRangeThreeMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <element id="pacb_SummaryOfSignificantAccountingPoliciesLineItems" name="SummaryOfSignificantAccountingPoliciesLineItems" nillable="true" type="xbrli:stringItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <element id="pacb_SummaryOfSignificantAccountingPoliciesTable" name="SummaryOfSignificantAccountingPoliciesTable" nillable="true" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" abstract="true" xbrli:periodType="duration" />
  <element id="pacb_TwoThousandTenEquityIncentivePlanMember" name="TwoThousandTenEquityIncentivePlanMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_ProceedsFromIssuanceOfCommonStockNetOfIssuanceCosts" name="ProceedsFromIssuanceOfCommonStockNetOfIssuanceCosts" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="debit" />
  <element id="pacb_DebtInstrumentInterestAndDiscount" name="DebtInstrumentInterestAndDiscount" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <element id="pacb_CustomerMember" name="CustomerMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_NotesMember" name="NotesMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_DebtAgreementHoldersMayElectToReceiveNetProceedsFromFinancingActivitiesPercentage" name="DebtAgreementHoldersMayElectToReceiveNetProceedsFromFinancingActivitiesPercentage" nillable="true" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_SupplementalBalanceSheetComponentsDisclosureAbstract" name="SupplementalBalanceSheetComponentsDisclosureAbstract" nillable="true" type="xbrli:stringItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <element id="pacb_LongTermDebtMaturitiesRepaymentsOfDebtIncludingInterestAndPrincipal" name="LongTermDebtMaturitiesRepaymentsOfDebtIncludingInterestAndPrincipal" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="credit" />
  <element id="pacb_EmployeeStockPurchasePlanMember" name="EmployeeStockPurchasePlanMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_LongTermRestrictedCashFairValueDisclosure" name="LongTermRestrictedCashFairValueDisclosure" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <element id="pacb_TransferOfInventoryToPropertyAndEquipment" name="TransferOfInventoryToPropertyAndEquipment" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="debit" />
  <element id="pacb_AdditionalLiabilityAssociatedWithIndemnificationObligations" name="AdditionalLiabilityAssociatedWithIndemnificationObligations" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="credit" />
  <element id="pacb_DebtInstrumentAggregatePrincipalAmount" name="DebtInstrumentAggregatePrincipalAmount" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="credit" />
  <element id="pacb_UnderwrittenPublicEquityOfferingMember" name="UnderwrittenPublicEquityOfferingMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_PercentageCommissionOfGrossProceedsOnSaleOfCommonStock" name="PercentageCommissionOfGrossProceedsOnSaleOfCommonStock" nillable="true" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_OptionToPurchaseAdditionalCommonStockUnderwritingAgreementPeriod" name="OptionToPurchaseAdditionalCommonStockUnderwritingAgreementPeriod" nillable="true" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_AdditionalCommonStockSharesAuthorizedUnderwritingAgreement" name="AdditionalCommonStockSharesAuthorizedUnderwritingAgreement" nillable="true" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" />
  <element id="pacb_CommonStockSharesAuthorizedUnderwritingAgreement" name="CommonStockSharesAuthorizedUnderwritingAgreement" nillable="true" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" />
  <element id="pacb_AmountOfCommonStockPreferredStockDepositorySharesWarrantsUnitsOrDebtSecuritiesAvailableInFuturePublicOfferings" name="AmountOfCommonStockPreferredStockDepositorySharesWarrantsUnitsOrDebtSecuritiesAvailableInFuturePublicOfferings" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="credit" />
  <element id="pacb_CommonStockPreferredStockDepositorySharesWarrantsUnitsOrDebtSecuritiesAvailableInFuturePublicOfferingsPeriodFromEffectiveDate" name="CommonStockPreferredStockDepositorySharesWarrantsUnitsOrDebtSecuritiesAvailableInFuturePublicOfferingsPeriodFromEffectiveDate" nillable="true" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_FacilityAgreementMember" name="FacilityAgreementMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_RestrictedStockUnitsRsusWithTimeBasedVestingMember" name="RestrictedStockUnitsRsusWithTimeBasedVestingMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_RestrictedStockUnitsRsusWithPerformanceBasedVestingMember" name="RestrictedStockUnitsRsusWithPerformanceBasedVestingMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_SummaryOfRevenueByCategoryTableTextBlock" name="SummaryOfRevenueByCategoryTableTextBlock" nillable="true" type="nonnum:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_TimeBasedRestrictedStockUnitsRsusMember" name="TimeBasedRestrictedStockUnitsRsusMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_PerformanceBasedRestrictedStockUnitsRsusMember" name="PerformanceBasedRestrictedStockUnitsRsusMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_ShareBasedCompensationAwardTrancheOneTwoThreeAndFourMember" name="ShareBasedCompensationAwardTrancheOneTwoThreeAndFourMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_ServiceAndOtherMember" name="ServiceAndOtherMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_ScheduleOfOrganizationConsolidationAndPresentationOfFinancialStatementsTable" name="ScheduleOfOrganizationConsolidationAndPresentationOfFinancialStatementsTable" nillable="true" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" abstract="true" xbrli:periodType="duration" />
  <element id="pacb_OrganizationConsolidationAndPresentationOfFinancialStatementsLineItems" name="OrganizationConsolidationAndPresentationOfFinancialStatementsLineItems" nillable="true" type="xbrli:stringItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <element id="pacb_CashCashEquivalentsAndInvestmentsExcludingRestrictedCash" name="CashCashEquivalentsAndInvestmentsExcludingRestrictedCash" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <element id="pacb_IlluminaFcOpsCorpMember" name="IlluminaFcOpsCorpMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_PacificBiosciencesOfCaliforniaInc.Member" name="PacificBiosciencesOfCaliforniaInc.Member" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_UsGovernmentCorporationsAndAgenciesSecuritiesNotIncludedWithCashAndCashEquivalentsMember" name="UsGovernmentCorporationsAndAgenciesSecuritiesNotIncludedWithCashAndCashEquivalentsMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_LongTermRestrictedCashMember" name="LongTermRestrictedCashMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_CashCashEquivalentsAndInvestmentsMember" name="CashCashEquivalentsAndInvestmentsMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_NumberOfNoteHoldersPaid" name="NumberOfNoteHoldersPaid" nillable="true" type="xbrli:positiveIntegerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_NumberOfOfferings" name="NumberOfOfferings" nillable="true" type="xbrli:positiveIntegerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_PunitiveClassActionUnitedStatesDistrictCourtForNorthernDistrictOfCaliforniaMember" name="PunitiveClassActionUnitedStatesDistrictCourtForNorthernDistrictOfCaliforniaMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_IndividualClaimUnitedStatesDistrictCourtForNorthernDistrictOfCaliforniaMember" name="IndividualClaimUnitedStatesDistrictCourtForNorthernDistrictOfCaliforniaMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_PunitiveClassActionUnitedStatesDistrictCourtForDistrictOfDelawareMember" name="PunitiveClassActionUnitedStatesDistrictCourtForDistrictOfDelawareMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_GoingConcernPolicyPolicyTextBlock" name="GoingConcernPolicyPolicyTextBlock" nillable="true" type="nonnum:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_OperatingLeaseRightOfUseAssetAmortization" name="OperatingLeaseRightOfUseAssetAmortization" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="debit" />
  <element id="pacb_LesseeOperatingLeaseDescriptionTableTextBlock" name="LesseeOperatingLeaseDescriptionTableTextBlock" nillable="true" type="nonnum:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_BalanceSheetClassificationAbstract" name="BalanceSheetClassificationAbstract" nillable="true" type="xbrli:stringItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <element id="pacb_ObrienDriveMenloParkCaliforniaMember" name="ObrienDriveMenloParkCaliforniaMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_SingaporeAndEngineeringSupportFacilitiesInAllenTexasMember" name="SingaporeAndEngineeringSupportFacilitiesInAllenTexasMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_CommitmentsAndContingenciesLineItems" name="CommitmentsAndContingenciesLineItems" nillable="true" type="xbrli:stringItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <element id="pacb_CommitmentsAndContingenciesTable" name="CommitmentsAndContingenciesTable" nillable="true" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" abstract="true" xbrli:periodType="duration" />
  <element id="pacb_InstrumentMember" name="InstrumentMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_ConsumableMember" name="ConsumableMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_ContractWithCustomerLiabilityNoncurrentRecognitionPeriod" name="ContractWithCustomerLiabilityNoncurrentRecognitionPeriod" nillable="true" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_ReverseTerminationFeeReceivableRequiredUponTerminationOfMergerAgreementUnderCertainSpecifiedCircumstances" name="ReverseTerminationFeeReceivableRequiredUponTerminationOfMergerAgreementUnderCertainSpecifiedCircumstances" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <element id="pacb_ShareInstrumentNumberOfSharesConversionRatio" name="ShareInstrumentNumberOfSharesConversionRatio" nillable="true" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_InventoryTransferredFromPropertyAndEquipment" name="InventoryTransferredFromPropertyAndEquipment" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="credit" />
  <element id="pacb_CertifiedDepositsMember" name="CertifiedDepositsMember" nillable="true" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_NetCashProvidedByUsedInOperatingActivitiesExcludingRestrictedCash" name="NetCashProvidedByUsedInOperatingActivitiesExcludingRestrictedCash" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="debit" />
  <element id="pacb_MergerAgreementPeriodInWhichCompanyMustRepayContinuationAdvancesIfChangeOfControllTransactionIsEnteredIntoWithThirdParty" name="MergerAgreementPeriodInWhichCompanyMustRepayContinuationAdvancesIfChangeOfControllTransactionIsEnteredIntoWithThirdParty" nillable="true" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <element id="pacb_MergerAgreementContinuationAdvancesRepayableMinimumCompanyMustRaiseInEquityOrDebtFinancingInSingleTransaction" name="MergerAgreementContinuationAdvancesRepayableMinimumCompanyMustRaiseInEquityOrDebtFinancingInSingleTransaction" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="credit" />
  <element id="pacb_MergerAgreementPossibleTerminationFee" name="MergerAgreementPossibleTerminationFee" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="debit" />
</schema>
