We investigated the regulatory effect of interleukin (IL) 10 on IL-12-inducible killer activity of blood mononuclear cells (MNC) of healthy subjects. IL-10 suppressed non-MHC-restricted killer activity induced by IL-12 in a dose-dependent manner. Cytotoxicity against Daudi cells of blood MNC activated with optimal dose (100 U/ml) of IL-12 was significantly suppressed from 36.6 +/- 6.8% (mean +/- SE) to 26.0 +/- 5.0% by 100 ng/ml of IL-10 (n = 5; P < 0.05) at an E/T ratio of 20. IL-10, however, did not suppress killer induction by IL-2 from blood MNC. On the other hand, IL-4, a known inhibitor of IL-2-mediated killer induction, had no effect on IL-12-mediated killer induction from blood MNC. Moreover, production of interferon-gamma by IL-12-stimulated MNC was suppressed by IL-10. Because the presence of IL-10 is reported in the tumor-growing site, these observations suggest that IL-10 acts as a key cytokine in the suppression of IL-12-mediated antitumor response in situ.