T-helper type-1 (Th1) and type-2 (Th2) cytokines, respectively, favor T-cell-mediated immunity and defense against intracellular pathogens or antibody-mediated immunity and defense against extracellular pathogens. Here we report that type-1 and type-2 cytokines also exert a regulatory effect on human monocyte survival. Interleukin-12 (IL-12) enhanced survival in long-term (10 days) cultures of adherent monocytes, whereas IL-10 induced death by apoptosis. In short-term cultures (2 days), the Th2 cytokines, IL-10 and IL-4, enhanced apoptosis; however, the Th1 cytokines, IL-12 and IL-2 only showed a reducing effect on monocyte apoptosis in culture conditions that decreased monocyte adhesion leading to increased levels of spontaneous apoptosis; finally, the Th1 cytokine, interferon-gamma (IFN-gamma), acted in a dose-dependent fashion: At high concentrations, IFN-gamma enhanced apoptosis, which is an effect related to IL-10 secretion and reduced by antibodies to IL-10. Th1 cytokines reduced monocyte apoptosis induced by several stimuli: IL-2 reduced apoptosis induced by either IL-10 or high concentrations of IFN-gamma, IL-12 reduced apoptosis induced by either the ligation of the Fas (CD95) molecule or gamma-irradiation, and IFN-gamma (at low doses that did not trigger apoptosis) reduced apoptosis induced by gamma-irradiation. These findings suggest that the regulatory role of type-1 and type-2 cytokines on the development of immune responses and inflammatory reactions also involves the regulation of monocyte death by apoptosis.