Abstract: Objective : To study the in vitro inhibitory effect of fludarabine and mitoxantrone on RPMI8226 and KM3multiple myeloma cell lines. Methods : MTT assay was used to observe the proliferation of RPMI8226 andKM3 cell lines treated with 1.25-20 μ g/ml fludarabine or a combination of fludarabine and mitoxantrone. Results : In the fludarabine group, the proliferation was increasingly inhibited as fludarabine dose wasincreased in both cell lines ( P <0.01). The inhibition was more significant in RPMI8226 and KM3 cell linestreated with fludarabine plus mitoxantrone than in those treated with fludarabine or mitoxantrone alone (P<0.01). Conclusion : The proliferation of RPMI8226 and KM3 cells was remarkably inhibited by fludarabine in adose-dependent manner in vitro. Fludarabine combined with mitoxantrone inhibited the proliferation ofRPMI8226 and KM3 cell lines even more markedly, providing an experimental basis for successful multiplemyeloma treatment.