A new cationic liposome formulation of sphingosine (SP) and dioleoylphosphatidylethanolamine (DOPE) was developed as an efficient transfection reagent. This SP/DOPE liposome showed efficient transfection in a wide variety of mammalian cancer cells. No significant cytotoxicity of the SP/DOPE liposome to cells was observed. The tranfection activity was greater than that of a well-reported liposome which was made from a cholesterol derivative 3beta-[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and the neutral lipid DOPE. In addition, the SP/DOPE liposome was found to be less toxic to cells than the DC-Chol/DOPE liposome. Stable transfections mediated by SP/ DOPE liposome were also demonstrated. These results suggest that the SP/DOPE liposome may provide a good gene delivery system to be used in the human cancer gene therapy.