A diet containing 0.4% DHEA was fed to male mice of a long-lived strain from 3 weeks until 18 weeks of age. These mice were compared with others fed a control diet ad libitum and with mice pair-fed the control diet in amounts approximating the intake of the DHEA-fed group. Mice fed the DHEA diet failed to eat all of the food presented to them whereas the pair-fed mice ate all of their food. All mice were studied at 18 weeks of age for two age-sensitive immune parameters (spleen lymphocyte proliferation induced by T-cell mitogens [PHA or ConA] and natural killer cell lysis of an allogeneic tumor). DHEA feeding led to: 1) a decrease in food intake (approximately 30% less than for mice fed the control diet ad libitum), 2) a lower body weight at 18 weeks of age (approximately 40% lower than for ad libitum controls) due to a decrease in the body weight gained from 3 weeks through 18 weeks of age (approximately 55% lower than controls), 3) a lower spleen weight (approximately 30% lower than controls) but without lower numbers of nucleated cells per spleen, 4) an increase in PHA-induced proliferation by spleen lymphocytes (approximately 100% higher than for controls) and, 5) no influence on splenic natural killer cell activity. The inhibition of body weight gain for mice fed DHEA appeared due to both a reduction in food intake and a metabolic effect since mice eating DHEA gained less body weight per gram of food eaten than did mice in either group eating the control diet.