Recent studies indicate that young female proestrus mice show an enhanced immune response following trauma-haemorrhage, as opposed to the immunodepression observed in males of comparable age. Testosterone is suggested as the cause of immunodepression in males, whereas oestradiol seems to be responsible for the enhanced immune response in females, however, sex hormone levels decrease with age. To determine if the sexual dimorphism in immune responses observed in young mice following trauma-haemorrhage changes with age, young (2-3 months) and aged (18-19 months) male and female CBA/J NIA mice were subjected to soft-tissue trauma (laparatomy) and haemorrhage (35 + 5 mmHg for 90 min and fluid resuscitation) or sham operation. Mice were killed 24 h later, and whole blood, as well as splenic and peritoneal macrophages (Mφ) obtained. Plasma 17β-oestradiol and free testosterone decreased in aged females and males, respectively. Mφ from young females had enhanced IL-1β and suppressed IL-10 production following trauma-haemorrhage, while aged females had unchanged production IL-1β and IL-6 production and enhanced IL-10 release. In contrast, IL-1β and IL-6 production by Mβ from young males was suppressed and IL-10 production enhanced following trauma-haemorrhage, whereas Mφ from aged males produced elevated levels of IL-1β and IL-6 and suppressed levels of IL-10 following trauma-haemorrhage. Thus, the gender-related changes in the immune response to trauma-haemorrhage were reversed in aged mice.