We have studied the effect of immune complexes (IC) on interleukin (IL)‐12 secretion by human monocytes in vitro. Two experimental models of IC were used. IC formed of tetanus toxoid and polyclonal anti‐tetanus toxoid antiserum as well as heat‐aggregated human serum IgG almost completely inhibited IL‐12 (p70 and p40) secretion induced by interferon‐γ and lipopolysaccharide in human blood‐derived monocytes. Neutralizing anti‐IL‐10 antibodies plus indomethacin restored IL‐12 secretion in the presence of IC to a high extent, indicating that IL‐10 and prostaglandin (PG) partially mediate the IC‐induced inhibition of IL‐12 secretion. However, neutralization of tumor necrosis factor (TNF)‐α by specific antibodies also incompletely restored IL‐12 secretion. Indeed, monocytes secrete high levels of TNF‐α upon stimulation by IC. We found that exogenously added TNF‐α caused a profound inhibition of monocytic IL‐12 secretion in the absence of IC, again mediated via the induction of IL‐10 and PG. In summary, IC inhibit IL‐12 secretion via TNF‐α‐induced IL‐10 and PG synthesis. We conclude that IC, typically appearing in the course of chronic inflammatory processes, may influence the balance between Th1 and Th2 responses and may thus contribute to a deprivation of cell‐mediated immune responses.