Immunity declines with advancing age. Lymphocyte proliferation, natural killer cell activity, and antibody response to tetanus toxoid vaccination were evaluated in cohorts of rhesus monkeys (Macaca mulatta) aged 2–36 years in order to characterize senescent changes in immune function. The results were analyzed in accordance with host age. Lymphocyte proliferation was generally low in older monkeys, especially males. Lymphocytes from old male monkeys responded significantly less to test mitogens than did those of old female (P<.05) or young males and females (P<.01). Natural killer cell function was similarly decreased in old monkeys; however, for this function there was no apparent gender difference. Antibody response to tetanus vaccine was less in older monkeys but was also low in several of the younger moskeys. These data confirm our expectation that, like other mammalian species, the rhesus monkey shows a decline in immune function with age and demonstrate further that the changes are more marked in males. Rhesus monkeys, therefore, are suitable for the investigation of mechanisms of immune senescence.