OBJECTIVE To explore the chemotherapeutic susceptibility of SP cells in human pulmonary adenocarcinoma cell line A549 and the possible mechanism of multidrug resistance.METHODS SP and non-SP (NSP) cells in the cell line A549 were isolated by fluorescence activated cell sorter. The susceptibility of SP and NSP cells to DDP, 5-FU, VP16, NVB and GEM was detected by a drug susceptibility test, and IC50s were calculated 24 h a er the chemotherapy; and then a er a 2-hour IC50 treatment with 5 chemotherapeutic drugs on the 2 subsets of NSP cells, the intracellular drug levels were determined and analyzed using high performance liquid chromatograph.RESULTS There was no statistical signifi cance in comparison of the di. erences in IC50s and in intracellular drug levels a er DDP treatment between the 2 subsets (P > 0.05), (P > 0.05). However,all IC50s of the other 4 drugs were significantly higher in the SP cells than in the NSP cells (P < 0.01). A er the chemotherapy, the intracellular drug levels of the other 4 drugs were significantly lower in SP cells than in NSP cells (P < 0.01).CONCLUSION Compared to NSP cells, SP cells in the cell line A549 have stronger resistance to the chemotherapeutics. The multidrug resistance of SP cells closely correlates with the function of SP cells discharging chemotherapeutic agents.