Liposomes may exert certain toxic effects on human cells depending on their composition and concentration when used as drug carriers. In this study, the behaviour of human fibroblasts in the presence of soya phosphatidylcholine (soya-PC) liposomes and the effect of the incorporation of vitamin E into the membrane of such liposomes, was investigated. Human fibroblasts were incubated for 72 h with low (50 mu M) and high (200 mu M) concentrations of large, unilamellar (LUV) soya-PC liposomes in the presence and absence of vitamin E (soya-PC:vitamin E; 10:0.5). The resulting cultures were studied by scanning and transmission electron microscopy, fluorescence microscopy and labelling with rhodamine B. The large unilamellar soya-PC liposomes obtained were of mean diameter 86.4 nm (soya-PC) and 78.3 nm (soya-PC:vitamin E). No significant changes in cell viability were observed between untreated fibroblasts and those incubated with 50 mu M soya-PC liposomes. In contrast, a marked loss of cells was apparent at a concentration of 200 mu M soya-PC liposomes which was reversible by the addition of vitamin E. Morphological changes including the production of microvilli or ＇bubbling＇ of the cell membrane, were incurred by some of the fibroblasts on addition of soya-PC liposomes. The addition of vitamin E did not affect the changes produced at the lower liposome concentrations but was able to reduce the cytotoxic effects occurring at higher concentrations, possibly by inhibiting the formation of liposome aggregates. The use of PC-soya liposomes containing vitamin E at high concentrations is proposed as a means of delivering high doses of drugs.