Although haemorrhagic shock produces immunodepression in both humans and experimental animals, no information is available concerning gender differences in the immune and endocrine response to shock. To study this, male and female (proestrus and diestrus) C3H/HeN mice (25 g body weight) were bled and maintained at a mean arterial blood pressure of 35 ± 5 mmHg for 1 h and then adequately resuscitated. The animals were killed at 2 h after resuscitation to obtain splenocytes, macrophages (Mo, peritoneal and splenic), as well as whole blood. IL-1 release by Mo, splenocyte proliferative capacity and splenocyte IL-3 release in female mice was significantly increased. Male mice, however, showed decreased release of all interleukins (IL-1, 2, 3, 6) as well as splenocyte proliferative capacity after shock. Plasma corticosterone levels decreased in proestrus female mice, as opposed to increased levels in males following shock. Corticosterone may therefore, be in part responsible for the observed gender differences. To the authors' knowledge, this is the first study which shows that immune responsiveness in female mice is enhanced after haemorrhagic shock, as opposed to decreased responsiveness in males. Thus, unlike males which exhibit increased susceptibility to sepsis/infections, females should be able to better tolerate the deleterious effects of shock.