A plasmid, pActDTA, whose expression is fatal to mammalian cells, caused a decrease in HeLa cell survival only if the plasmid was encapsulated in egg PC liposome whose surface was modified with a poly(ethylene glycol) derivative bearing two alkyl chains (abbreviated as PEG-lipid). This result suggests that the reconstitution of PEG-lipid into the liposome made direct transport of the plasmid into the cytosol of the cell by a mechanism other than endocytosis possible. Furthermore, a transmission electron micrographic observation showed that the interaction between HeLa cell and the PEG-lipid reconstituted liposome was consistent with fusion. This interaction was unique to the PEG-lipid reconstituted liposome. These results strongly suggest that this be the first example of PEG-lipid induced fusion of liposome to a mammalian cell and support the validity of the PEG-lipid reconstituted liposome as a fusogenic liposome to a mammalian cell.