Background: Free radical-mediated oxidative stress has been implicated in the genesis and progression of atherosclerosis. Methods: The lipid peroxides and antioxidant status of various tissues were investigated in hypercholesterolemic rats and the effect of vitamin E supplementation on defense systems. Results: Cholesterol-feeding caused a significant increase in the lipid peroxide concentrations of plasma, erythrocytes, liver and brain. In addition, a significant decrease in glutathione (GSH) content, glutathione peroxidase (GSH-Px) and glutathione transferase (GSH-ST) activities were found in erythrocytes and liver but superoxide dismutase (SOD) activity remained unchanged in these tissues in comparison to the control group. Vitamin E supplementation to hypercholesterolemic rats induced a significantly decrease in lipid peroxide concentrations and a significant increase in the GSH content, GSH-Px and GSH-ST activities in erythrocytes and liver. Conclusions: Long-term administration of vitamin E may play an important role in suppressing oxidative stress, and thus, may be useful for the prevention and/or early treatment of hypercholesterolemia. (C) 2002 Elsevier Science B.V. All rights reserved.