Experiments were performed to investigate the change of hepatic T4 5'-deiodination and the preventive effects of selenium (Se) and vitamin E in rats fed grains from a Keshan disease (KD) endemic area. The results showed that consumption of the endemic grain for 8 weeks caused a significant reduction in hepatic T4 5'-monodeiodinase and glutathione peroxidase activities, and a marked enhancement of hepatic malondialdehyde content. These changes could be effectively prevented through Se or vitamin E supplementation to the diet. These observations confirm the reduced ability of hepatic T4 5'-deiodination induced by the pathogenic factors existing in the endemic grains, and the preventive effects of selenium and vitamin E on the alterations. The present study suggests that the reduction in hepatic T4 deiodination in these animals may be the consequence of hepatic damage owing to uncontrolled free radical metabolism, and that the relative deficiency of vitamin E, besides selenium deficiency, may also play a role in the pathogenesis of KD.