The production of the second complement component (C2) by human monocytes in culture was inhibited by increasing their intracellular concentrations of cAMP following the addition to the culture medium of dibutyryl-cyclic AMP, 8-bromo-cyclic AMP, theophylline, isobutylmethylxanthine, cholera toxin or adenosine. The effects were not due to cytotoxicity or loss of cells from the monolayers, and therefore must reflect a decreased synthesis of section of C2. Although dibutyryl-cyclic GMP enhanced C2 production, 8-bromo-cyclic GMP, ascorbic acid and sodium nitroprusside did not have this effect. These observations suggest that the action of dibutyryl-cyclic GMP is not due to elevation of cyclic GMP levels and that cyclic GMP levels do not play a major role in C2 production by monocytes.