Several aspects of T cell-mediated immune responses decline with age, but it is not known how gender affects this decline. Using 3- and 26-month-old male and female Fischer 344 rats, we examined the effects of sex and age on four different immune events that normally decline during aging: antibody synthesis to a T-dependent antigen, lectin-induced proliferative responses, IL-2 synthesis, and natural killer activity. We found that all these responses decreased with age. Spleen cells from aged females had higher spontaneous, phytohemagglutinin (PHA), and concanavalin A (Con A)-induced proliferative responses, and a two-fold increase in IL-2 synthesis than aged males, although no differences in these responses were evident between young males and females. Both natural killer (NK) activity and the ability to generate plaque-forming cells to sheep erythrocytes (SRBC) declined with age, but there were no differences between males and females for these responses in either age group. These data indicate that sex-associated differences in IL-2 synthesis and spontaneous and lectin-induced proliferative responses that are not detected in young animals become evident with advancing age.