To determine whether vitamin E protects against thyroxineinduced oxidative stress in heart and soleus (slow oxidative) muscles, lipid peroxide (thiobarbituric acid-reactive substances) and antioxidant enzymes were measured in those tissues of hyperthyroid rats supplemented with vitamin E. The rats were rendered hyperthyroid by the administration of L-thyroxme in their drinking water. In experiment (EXPT) 1, 30 mg/kg/dose of alpha-tocopheryl acetate was administered to the vitamin E-treated group. In EXPT II, the rats were fed a diet containing either <1 IU/kg (deficient diet), 20IU/kg (control E diet), or 500IU/kg (high E diet) of vitamin E and hyperthyroidism was induced. In EXPT I, hyperthyroidism induced an increase in oxidative enzymes, mitochondrial superoxide dismutase and lipid peroxide level, and a decrease in cytosolic superoxide dismutase, glutathione peroxidase and catalase in both tissues. Vitamin E treatment inhibited the increase in lipid peroxide level totally in the heart and partially in the soleus, with minimal changes in the other biochemical indices studied. In EXPT II, the lipid peroxide level was markedly increased in both tissues of the vitamin E-deficient group, and decreased in those of the group fed high E diet. There were some adaptive changes in the levels of cytosolic superoxide dismutase, glutathione peroxidase, and catalase in response to vitamin E deficiency, whereas neither oxidative enzymes nor mitochondrial superoxide dismutase were altered. These results suggest that vitamin E protects against lipid peroxidation in hyperthyroid heart and skeletal muscle independently of the changes in oxidative enzymes and antioxidant enzymes.