This study evaluated the effects of dietary vitamin A and E on the in vitro capacity of blood mononuclear leukocytes from calves to produce nitric oxide. Calves fed milk replacer received 100 IU/d of vitamin E as RRR-alpha-tocopherol or RRR-alpha-tocopheryl acetate and 0, 1700, 34,000, or 68,000 IU of vitamin A as retinyl acetate. Leukocytes from calves produced greater amounts of nitric oxide relative to leukocytes from adult cattle. The greater production of nitric oxide by calf leukocytes may be typical of the immature neonatal immune system. Nitric oxide production by calves fed RRR-alpha-tocopherol and either 1700 or 34,000 IU of vitamin A was less than that of calves in other groups and was more typical of production by leukocytes from cows. Our data suggest that optimal amounts of dietary vitamins A and E prompt the maturation of this response toward one that is more typical of adult cattle. Leukocytes from 1-wk-old calves produced less nitric oxide and were less responsive to stimuli than were leukocytes from older calves, a possible consequence of suppressive factors that were present in the ingested colostrum or in the circulation at birth.