BACKGROUND: The possibility that anesthesia may alter the course of an infection has been under consideration for more a century. Alterations have been found in every component of the immune response during anesthesia and surgery. In this work, we have investigated the effect of lidocaine and propofol on interleukin-2 (IL-2), interleukin-4 (IL-4), and nitric oxide (NO) production in mice. METHODS: The culture supernatants of splenocytes exposed with anesthetics and lipopolysaccharide (LPS), or sera from mice injected with these agents were harvested to assay IL-2, IL-4, and NO. RESULTS: We detected that IL-2 productions of splenocytes culture supernatants and mice sera after exposure with lidocaine or propofol were decreased while IL-4 productions were increased. In addition, NO of mice sera was increased after lidocaine or propofol exposures. CONCLUSIONS: These findings suggest that lidocaine and propofol interfere with IL-2, IL-4, and NO production. This may explain the clinically well-recognized disturbance of human immunity after surgery and anesthesia.