Selenium and vitamin E deficiencies were studied as part of an evaluation of oxidant defenses in guinea pigs. Male guinea pigs (100-120 g) were fed a control diet (C) or the diet without selenium (0 Se), without vitamin E (0 E), or without either selenium or vitamin E (0 Se-0 E). Between d 30 and 35, 7 of 13 guinea pigs fed the 0 Se-0 E diet were euthanized because of severe weakness of their extremities. No guinea pigs in the other diet groups developed weakness. Guinea pigs from each group were killed on d 37. Selenium deficiency and vitamin E deficiency were verified by measurement of glutathione peroxidase and alpha-tocopherol. Creatine phophokinase (CPK) activity was greater than controls in both groups fed vitamin E-deficient diets, but the increase was greater in the 0 Se-0 E group than in the 0 E group. Muscle F(2)-isoprostanes were greater than controls in both groups fed vitamin E-deficient diets with the level in the 0 Se-0 E group greater than that in the 0 E group. Histologic muscle necrosis was severe in the 0 Se-0 E group, minimal in the 0 E group and absent from other groups. The diets used in this study induced selenium and vitamin E deficiencies in guinea pigs. The study demonstrates that combined selenium and vitamin E deficiency results in a fatal myopathy in guinea pigs that is associated with lipid peroxidation in the affected muscle. This nutritional myopathy is much more severe than the myopathy that occurs with vitamin E deficiency alone.