We have examined the ability of a commonly used fullerene, C60, to induce oxidative damage on photosensitization using rat liver microsomes as model membranes. When C60 was incorporated into rat liver microsomes in the form of its cyclodextrin complex and exposed to UV or visible light, it induced significant oxidative damage in terms of (1) lipid peroxidation as assayed by thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides and conjugated dienes, and (2) damage to proteins as assessed by protein carbonyls and loss of the membrane-bound enzymes. The oxidative damage induced was both time- and concentration-dependent. C60 plus light-induced lipid peroxidation was significantly inhibited by the quenchers of singlet oxygen ((1)O2), beta-carotene and sodium azide, and deuteration of the buffer-enhanced peroxidation. These observations indicate that C60 is an efficient inducer of peroxidation and is predominantly due to (1)O2. Biological antioxidants such as glutathione, ascorbic acid and alpha-tocopherol significantly differ in their ability to inhibit peroxidation induced by C60. Our studies, hence, indicate that C60, on photosensitization, can induce significant lipid peroxidation and other forms of oxidative damage in biological membranes and that this phenomenon can be greatly modulated by endogenous antioxidants and scavengers of reactive oxygen species.