The effect of nitecapone (3[(3,4-dihydroxy-5-nitrophenyl) methylene]-2,4-pentanedione) on lipid peroxidation in guinea pig liver microsomes was assessed with the thiobarbituric acid assay. Nitecapone inhibited dose-dependently hydroxyl and peroxyl radical induced lipid peroxidation with IC50-values of 11.1 microM and 16.2 microM, respectively. Nitecapone was an effective antioxidant in native microsomes, where it potentiated glutathione-dependent protection against oxidative stress. Nitecapone provided dose-dependent reduction in lipid peroxidation lasting up to three hours in the presence of glutathione. The long-lasting effect was lost, when the microsomes were boiled. These data suggest that nitecapone is an effective scavenger of oxygen derived free radicals, and that its antioxidant properties are potentiated by glutathione.