Postischemic organ dysfunction is influenced by gender and sexual steroids. To compare the susceptibility of the kidney to postischemic failure between sexes, the left vascular pedicle was clamped for 50 minutes in anesthetized male and female Wistar rats. Survival rate, renal and systemic hemodynamics and renal prepro-endothelin (pp-ET) mRNA expression were measured. Eight percent of males as compared to 75% of females survived for more than 7 days. Previous orchidectomy of mature rats or sexual immaturity improved the rate of 7 day survival to 67% and 58%, respectively, as compared to intact males (P < 0.05). Estradiol treatment of mature male animals also resulted in a significantly better survival. Ovariectomy, sexual immaturity or testosterone treatment had no impact on the course of renal failure in females. The early postischemic recovery of renal blood flow was delayed due to a dramatic increase in renal vascular resistance in male versus female rats. The expression of pp-ET gene in the kidneys was increased at 5 minutes following reperfusion and was significantly higher 2 hours after ischemia in males, but not in females. Pretreatment with the endothelin A receptor antagonist LU 135252 provided indistinguishable survival rates in intact male and female rats after warm renal ischemia. Female rats enjoy relative protection against postischemic renal failure. Furthermore, in intact males the effects of androgens upon ischemic kidney damage seem to be mediated by endothelin-induced vascular changes.