Objective: To determine the effects of: a) surgical trauma, b) crystalloid resuscitation, and c) different durations of hypotension on cellular immunity after hemorrhagic shock. Design: Prospective, multiexperimental, randomized, controlled studies. Setting: University research laboratory. Subjects: Inbred C3H/HeN (endotoxin-sensitive) mice, aged 6 to 7 wks, weighing 18 to 23 g. Interventions: Crystalloid resuscitation, with and without blood, after hemorrhage. Measurements and Main Results: Mice which did or did not undergo laparotomy were subjected to hypotension of 35 mm Hg for 60 or 90 mins. Crystalloid resuscitation with and without blood was then provided. Animals were killed at 2 hrs after hemorrhage and cytokine concentrations in supernatants of splenocytes, splenic macrophages, and serum were assessed by bioassays. The cellular release of interleukin (IL)-2, IL-3, IL-6, tumor necrosis factor, and the splenocyte proliferative capacity were significantly and similarly depressed in all groups. Conversely, circulating IL-6 concentrations were significantly increased in all groups. Conclusions: Cellular immunity was depressed at 2 hrs after simple hemorrhage and no further depression occurred if hemorrhage was coupled with trauma, pure crystalloid resuscitation was provided, or the shock period was prolonged. Thus, the early immunodepression after hemorrhage was mainly dependent on the severity rather than the duration of shock, resuscitation regimen, or tissue trauma.