Feeding a high fish oil diet (25 wt%) to rats for 14 days increased the content of docosahexaenoic acid (DHA) in liver lipids, and diminished the liver antioxidant defenses as measured by the contents of alpha-tocopherol, ascorbic acid and non-protein SH, the last of which is consisting mostly of glutathione, and the activity of selenium-dependent glutathione peroxidase (GSHPx). These changes in antioxidant defenses are suggested to be associated with an increased susceptibility of the liver to lipid peroxidation as assessed by thiobarbituric acid (TBA) reaction and chemiluminescence intensity. Serum TBA value was also high in the rats given high fish oil diet. The present results demonstrate that a high fish oil diet potentiates susceptibility of rats to lipid peroxidation and augments requirement for antioxidants to provide adequate protection.