Iodine and selenium are essential components of normal thyroid hormone metabolism and are involved in the modulation of antioxidant defense system. This study was designed to evaluate the extent of peroxidation of lipids and activities of antioxidant enzymes (AOEs) in various tissues of iodine- and/or selenium-deficient rats in relation to thyroid hormone metabolism. Iodine deficiency caused marked enhancements in glutathione peroxidase (GSHPx), superoxide dismutase (SOD), and catalase (CAT) activities in thyroid but did not cause lipid peroxidation (LP), indicating the occurrence of an adaptive response that protected the gland against oxidative stress induced by high levels of thyroid stimulating hormone (TSH). Except significant reduction in CAT activity in liver and kidney and an enhancement of SOD in kidney, iodine deficiency did not cause any other alterations in other tissues. Selenium deficiency and combined iodine and selenium deficiency caused significant alterations in AOE activities in all tissues and caused significantly high levels of LP in thyroid, liver, brain, and plasma, but not in kidney. Alterations in selenium-involved deficiencies appeared to be mainly caused by substantial losses of GSHPx activity; however, compensatory changes in SOD and CAT activities were also observed. © 2004 Wiley-Liss, Inc.