Fingerling channel catfish Ictalurus punctatus were fed purified diets either unsupplemented and deficient in both selenium and vitamin E, deficient in either selenium or vitamin E, adequate in both selenium (0.2 mg/kg) and vitamin E (60 mg/kg), or excessive in both nutrients (four times the recommended levels). After 115–120 d of feeding the experimental diets, the red blood cell membranes offish fed diets deficient in vitamin E were more susceptible to peroxidation than were those of fish fed diets that met or exceeded vitamin E recommendations. Hepatic, selenium-dependent glutathione peroxidase activity was suppressed in fish fed diets deficient in selenium when compared with this enzyme activity in fish fed diets containing recommended or higher levels of selenium. Intracellular superoxide anion production of macrophages was higher in fish fed the diet fortified with four times the recommended levels of both nutrients than in fish fed the other diets. None of the results indicated that selenium and vitamin E were complementing each other or that one nutrient was compensating for a deficiency of the other. The results of this study support the presently recommended levels of selenium and vitamin E for channel catfish diets and indicate that higher-than-recommended levels of one or both nutrients may enhance macrophage function.