A number of clinical studies have shown that multiple and severe trauma causes immunosuppression and increases the susceptibility to sepsis. However, because there is a close temporal relationship between trauma and hemorrhage in humans, it is difficult to dissociate the effects of tissue trauma versus hemorrhage on immunity in the clinical setting. Studies in mice have shown that simple hemorrhage per se as well as laparotomy alone produces a marked depression in cellular immunity and no difference was seen in the extent of depression at 2 h if these two insults were combined. Nonetheless, it remains unknown whether the combined model of trauma-hemorrhage produces a more protracted depression in immune function. To study this, 5 days after either sham operation, laparotomy (i.e.trauma), hemorrhage alone (35 mmHg for 1 h, followed by resuscitation), or the combination of laparotomy and hemorrhage, mice (C3H/HeN) were sacrificed, after which splenocyte and peritoneal macrophage cultures were established. The proliferative capacity of the splenocytes, as well as their ability to release IL-2 and IL-3, was markedly decreased in the trauma-hemorrhage animals but was normal in the other groups. Furthermore, the release of IL-6 by peritoneal macrophages from animals that underwent trauma-hemorrhage was also significantly depressed. These results support the concept that traumatic injury in the form of a midline laparotomy combined with hemorrhage produces a more protracted impairment in cell-mediated immunity than laparotomy or hemorrhage alone. © 1995 The Shock Society.