Although numerous studies concerning the etiology of immunosuppression following various forms of trauma are being carried out, relatively little attention has been directed toward addressing the issue of whether simple hemorrhage per se plays a major role in producing the immunosuppression. The available information indicates that even transient hypotension in the absence of any significant tissue trauma produces a marked depression in both the specific and nonspecific cell-mediated immunity. This was evidenced by the depression of lymphocyte function, macrophage expression of receptors involved in opsonin-mediated phagocytosis, splenic production of interleukin 2, and antigen presentation function by peritoneal and splenic macrophages, as well as Kupffer cells. These alterations in immune function after hemorrhage occur without changes in lymphocyte population and subpopulation numbers. The depressions in various immune functions are apparent immediately after hemorrhage and they persist for a prolonged period of time despite volume resuscitation. While the dysfunctions in Kupffer cell antigen presentation and Ia expression are comparable with those found with peritoneal and splenic macrophages, the increases in inflammatory monokine production [tumor necrosis factor (TNF)], and consequently its release into the blood, are specific to Kuppfer cells. This depression in macrophage antigen presentation does not appear to be due to any elevation in serum endotoxin levels during or after hemorrhage. Although the precise mechanisms responsible for producing the immunodepression after simple hemorrhage and resuscitation remain unknown, the depression of macrophage antigen presentation, as well as the enhanced capacity of Kuppfer cells to produce TNF, may play an important role in initiating cell and organ dysfunction and in contributing to the host's enhanced susceptibility to sepsis after hemorrhage.