Anesthetic agents are believed to have an adverse effect on human immune defense mechanisms. We investigated changes in peripheral immune cell numbers such as natural killer (NK) cells, B cells, and T lymphocyte subpopulations (CD4+ and CD8+ cells) and differences in cytokine production after stimulation with different mitogens before and during narcosis. We studied 30 patients undergoing elective orthopedic surgery. Stimulatory experiments were performed with the mitogens lipopolysaccharide, phytohemagglutinin A, and inactivated Newcastle disease virus. During general anesthesia with fentanyl, thiopental, and isoflurane, there was a significant decrease of circulating NK cells in the peripheral blood accompanied by a significant increase of B cells and CD8+ T lymphocytes. We detected a significant anesthesia-associated increase of interferon (IFN)-gamma, IFN-alpha, tumor necrosis factor-alpha, and soluble interleukin-2 receptor (sIL-2R) synthesis after stimulation with different mitogens while interleukin (IL)-1 beta and IL-6 protein did not change significantly. After the beginning of surgery, CD8-positive cells showed a return to control values and NK cell number increased slightly. These findings suggest that general anesthesia interferes with immune cell number and immune cell response. This may explain the clinically well-recognized disturbance of human immunity after surgery and general anesthesia.