This study investigated the effects of three volatile anesthetics (sevoflurane, isoflurane, and enflurane) on cytokine release by human peripheral mononuclear cells (PBMCs) stimulated by natural killer (NK)-sensitive tumor cells, K562, in vitro. PBMCs, as effector cells, obtained from 31 volunteers were randomly allocated to two groups in the first set of experiments. One group was incubated with K562 (n = 21) and the other with medium alone as a control (n = 10). In a second set of experiments, PBMCs from each volunteer (n = 21) were divided into three groups: nonanesthetic, 1.5-MAC, and 2.5-MAC groups (n = 7 for each anesthetic). After 2 h exposure to anesthetic gas or air, K562 cells were added to the effector cells. After 4 h incubation, interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), and interferon-alpha (INF-alpha) in the supernatant were assayed. IL-1 beta and TNF-alpha levels were significantly increased in comparison with those in the control group. IL-2 levels tended to be higher than those in the control group. No effect on IFN-alpha levels was found. After anesthetic exposure, the releases of IL-1 beta and the release of TNF-alpha were significantly inhibited compared with those after air exposure. None of the anesthetics inhibited IL-2 release. The anesthetics studied are capable of altering the release of cytokines by NK and NK-like cells in response to tumor cells.