The activities of superoxide dismutase (SOD, EC 1.15.1.1), glutathione peroxidase (GPx, EC 1.11.1.9) and the levels of alpha-tocopherol and oxidized lipoproteins were investigated in the plasma of New Zealand rabbits either before or after cholesterol-diet induced hypercholesterolemia. Plasma SOD activity increased while GPx activity decreased after 60 days of cholesterol feeding. However, in the cholesterol-fed rabbits the release of superoxide dismutase fraction C from vasculature by heparin was lower than that in control rabbits. The levels of triglyceride hydroperoxides increased in low density and high density lipoproteins after feeding rabbits with the cholesterol-rich diet during 60 days. Also, a trend for increasing cholesteryl ester hydroperoxides was observed in beta-very low density and high density lipoproteins. An increase in alpha-tocopherol concentration (microM) was observed in very low density and low density lipoprotein fractions, but after normalization of these results to the cholesterol content of lipoprotein particles only the alpha-tocopherol content of low density lipoprotein remained higher after 60 days of cholesterol feeding. The data suggest that low glutathione peroxidase and superoxide dismutase fraction C activities may facilitate intravascular lipoprotein oxidation by oxidant species generated by the endothelium or blood cells.