The cell membrane is protected against lipid peroxidation by endogenous antioxidants such as vitamin E (alpha-tocopherol). The oxidised form of alpha-tocopherol (alpha-tocopherol quinone) does not have this antioxidant function. However, the literature indicates that alpha-tocopherol quinone can be reduced to alpha-tocopherol in vivo and thereby will add to the total antioxidant potential (Moore AN, Ingold KU. Free Radic Biol Med 1997;22:931-4). We found that GSH (reduced glutathione) did not mediate the reduction of alpha-tocopherol quinone, either directly in solution or in rat liver microsomes fortified with alpha-tocopherol quinone. This renders GSH a less likely candidate for alpha-tocopherol quinone reduction in vivo. In addition, alpha-tocopherol quinone did not enhance GSH-dependent protection against lipid peroxidation, either in control microsomes, or in vitamin E-extracted microsomes. Indeed, alpha-tocopherol quinone blocked GSH-dependent protection against lipid peroxidation in vitamin E-extracted microsomes. This indicates that alpha-tocopherol quinone can act as a pro-oxidant.