Previous studies have demonstrated that hemorrhagic shock produces immunodepression in young male mice, whereas the immunoresponsiveness in young proestrus female mice is enhanced under such conditions. This sexually dimorphic immune response to hemorrhage appears to be related to high estrogen and testosterone levels in females and males, respectively. Nonetheless, it is unknown what impact the age-related decline in the sex steroid levels has on the immune response after hemorrhage. To study this, young (2-3 mo) and aged (18-19 mo) male and female CBA/J NIA mice were subjected to laparotomy (i.e., soft tissue trauma) and hemorrhage (35 ± 5 mmHg for 90 min and fluid resuscitation) or sham operation. Twenty-four hours later, splenocyte responses were assessed in vitro. Splenic T lymphocyte responses [i.e., proliferation, interleukin-2 (IL-2) and interferon-γ (IFN- γ) release] were depressed in young males and enhanced in young females after trauma-hemorrhage. In contrast, in the aged male and female groups these parameters of splenocyte function were reversed after trauma-hemorrhage (i.e., increased proliferation and IL-2 release in aged males compared with suppressed proliferation and IFN-γ release in aged females). Furthermore, the release of the immunosuppressive cytokine IL-10 inversely correlated with the age- and gender-related changes in splenocyte responses after trauma- hemorrhage. Thus the sexually dimorphic immune response in young males and females to trauma-hemorrhage appears to reverse as sex hormone levels decline with age.