The purpose of this study was to investigate the effect of liposome composition, which affects the nature of vesicular membrane on the cytotoxic efficacy of bleomycin. Formulation A comprised phosphatidylcholine (PC), cholesterol (CH), and dicetylphosphate (DCP). Formulation B employed PC, CH with dioleoylphosphatidylethanolamine (DOPE) as the fusogenic component. Formulation C consisted of rigid liposomes comprising dipalmitoylphosphatidylcholine (DPPC), CH, and DCP. Preparation D contained dioleoylphosphatidylcholine (DOPC), CH, and DCP. Formulation E employed the same components of B, with PC being replaced with Pegylated PC. The cytotoxic efficacy was monitored using the Daudi cell line obtained from Burkitt's lymphoma. Formulations A and B significantly increased the cell death via necrosis compared with drug solution. Formulation D produced marginal increase in the efficacy of bleomycin with the rigid vesicles being similar to the control. Pegylated liposomes (E) were as effective as A and B, but the cytotoxic effect was via apoptosis. In conclusion, the efficacy of liposomes depended on the composition with fusogenic, flexible, or Pegylated vesicles being superior. Drug Dev Res 72: 265-273, 2011.