There is increasing evidence that islet beta cells may be susceptible to redox insult, and that this susceptibility may contribute to the pathogenesis of experimental models of diabetes mellitus. We investigated the effect of vitamin E deficiency, selenium deficiency, and combined deficiency on islet function and free radical scavenging systems. The tissue levels of glutathione peroxidase, catalase, and immunoreactive superoxide dismutases were measured in four groups of rats (i.e., controls and those with vitamin E, selenium, and combined deficiency). Glucose tolerance tests were performed for each animal before sacrifice. Superoxide dismutase concentrations in liver, heart, and skeletal muscle were within 20% of the control levels in all groups. However, the manganosuperoxide dismutase concentrations in islets were significantly lower than control levels in response to vitamin E, selenium, and combined deficiency. Combined deficiency appeared to have an additive effect. In contrast, cuprozinc superoxide dismutase concentration in islets was higher in the deficient groups than in controls. Insulin secretory reserve was decreased in each of the three deficient groups. This decrease was reflected as glucose intolerance only in the group with combined deficiency. Glutathione peroxidase activity was markedly decreased in selenium-deficient animals in all tissues studied. Catalase activity did not change significantly among groups in any tissue studied. Islets had the lowest glutathione peroxidase and cuprozinc and total superoxide dismutase levels among tissues studied.