Interferon gamma (IFN gamma) and interleukin 4, 10 and 12 (IL-4, -10, -12) production was measured in whole peripheral blood (WPB) and peripheral blood mononuclear cells (PBMC) of 10 chronic hepatitis C (CHC) patients. The level of IFN gamma in supernatants in mitogen-activated WPB was lower than in healthy donors. IL-10 served as a possible downregulative factor for IFN gamma, since its spontaneous IL-10 production was enhanced in CHC. Neutralization of IL-10 partly restored IFN gamma response in CHC patients. Recombinant IL-12 (rIL-12) also enhanced IFN gamma of CHC patients, but IL-12 production was decreased in CHC. Thus, IFN gamma production deficiency in CHC patients is secondary to blockage by high levels of IL-10-impaired IL-12 production.