The ability of leukocytes to kill tumor cells appears central to the defense against neoplastic growth. The authors determined the effect of thiopental on this phenomenon in vitro by incubating 51Cr-labelled YAAC-1 tumor cells obtained from the peritoneal cavities of syngeneic A/JAX white mice with immune leukocytes from the peritoneal cavities of allogeneic C57/black mice. Tumor-cell death was quantitated by the amount of 51Cr released into the medium following tumor-cell lysis. Thiopental, in concentrations used during routine anesthesia, inhibited tumor-cell killing in a dose-related manner. Inhibition of cytotoxicity ranged from 8.6 per cent at 2.8 x 10(-5) M thiopental to 38.1 per cent at 8.5 x 10(-5) M thiopental. Moreover, this inhibitory effect was additive to that previously demonstrated with halothane, and was related to the duration of exposure to the anesthetic. It is postulated that thiopental and other anesthetics contribute to the inhibition of leukocyte responsiveness observed in patients with malignancies who have undergone surgical procedures.