Serum levels of the interleukins (IL)-2, -1 beta, and -6, tumor-necrosis factor alpha (TNF-alpha), and prostaglandin E2 (PGE2) were measured serially before and after operation in patients undergoing various surgical procedures. Peripheral blood mononuclear cells (PBMC) from the same patients were analyzed before and after surgery for proliferative responses in the autologous mixed lymphocyte reaction (AMLR) and for cytolytic activity against the natural killer (NK)-sensitive K562 cell line. In patients who had major surgery, a decrease in IL-2 levels and increases in IL-1 beta, TNF-alpha, IL-6, and PGE2 levels were observed up to 9 days after the operation compared to those of the preoperative values. Decreased AMLR responses and NK activity were also observed in PBMC collected 5 days after surgery. All these changes were more intense in patients who had undergone major surgical procedures of increasing severity (i.e., cancer patients). Similar, although weaker, changes in cytokine serum levels, AMLR responses, and NK activity were also observed in patients undergoing minor surgery. Our data suggest that changes in cytokine serum levels may cause cellular immune dysfunctions, particularly in patients undergoing major surgery, and provide the basis for immune intervention in order to avoid infections occurring after major surgery.