The effect of murine IgG isotypes on the gene expression and secretion of the third component of complement (C3) has been studied using the monocytoid cell line P388D1 and oil-elicited mouse peritoneal macrophages. It is demonstrated that the binding of IgG2a and IgG2b but not IgG1 and IgG3 augments the biosynthesis of C3 both in the presence and in the absence of the phorbol ester, phorbol myristate acetate in the case of both cell types. The multifunctional cytokine interleukin-6 (IL-6) alone reveals no effect on the gene expression of C3, but increases the effectiveness of mouse IgG2a and IgG2b. Confirming the role of Fc gamma RII, a strong up-regulation of C3 gene expression and C3 secretion was found when macrophages were cultured with the F(ab')2 fragment of the Fc gamma RII-specific monoclonal antibody 2.4G2.