Although previous studies have shown that simple laparotomy produces a depression in peritoneal macrophage (Mφ) antigen presentation capacity, it remains unknown whether the adverse effects of laparotomy are limited to peritoneal Mφ or whether such an insult also affects splenocyte immune function. To study this, mice were anesthetized and a 1-inch midline abdominal incision was made, followed by abdominal closure. At 2 and 24 hours after the surgical procedure, the animals were killed, splenocyte cultures established and stimulated for 48 hours with concanavalin A (2.5 μg/mL), while peritoneal macrophage cultures were stimulated with LPS (10 μg/mL). The proliferative capacity of the splenocytes, as well as their ability to release interleukin-2 and interleukin-3, was markedly decreased at 2 as well as 24 hours after laparotomy. Furthermore, the release of interleukin-6 by splenic and peritoneal macrophages from animals that underwent laparotomy were also significantly depressed at both 2 and 24 hours. These results support the concept that surgical stress in the form of midline laparotomy per se is sufficient to produce a significant impairment in cell-mediated immunity, thus setting the stage for increased incidence of postoperative complications.