Previous studies have shown marked immunosuppression in males after trauma and hemorrhage. By contrast, immunosuppression was not evident in proestrous female animals. Further support for these findings came from studies demonstrating the immunosuppressive effects of male sex hormones and immunoenhancing effects of female sex hormones. In this regard, administration of 17β-estradiol or prolactin to male animals after trauma and hemorrhage significantly improved immune function. Furthermore, castration or androgen receptor blockade with flutamide after trauma and hemorrhage in male mice showed similar beneficial effects. Thus, regulation of sex hormone synthesis or their receptor activity appears to be a useful therapeutic approach for patients to cope with the deleterious sequelae of severe trauma and hemorrhage.