Cl inhibitor (Clinh), a member of the serine protease inhibitor gene superfamily, is a glycosylated plasma protein inhibiting the proteolytic activities of Clr and Cls and involved in the regulation of coagulation, fibrinolysis and kinin-releasing systems. In this study, the in vitro effect of androgen hormones, dehydroepiandrosterone (DHEA), testosterone (TEST) and recombinant human γ-interferon (γ-IFN), has been determined on the production of Clinh in human cell lines. In both human monocytoid/histiocytoid cell line U937 and in hepatoma derived cell line HepG2, DHEA and TEST upregulated the gene expression and secretion of Clinh. The most pronounced effect was detected in the concn range 10-7-10-9 M of the hormones. Under the same conditions DHEA and TEST had no detectable effect on the biosynthesis of C3, C2 and factor B by these cells, but DHEA at higher concn (10-4M) slightly increased that of C4 in HepG2 cells. Both in U937 and in HepG2 cells recombinant γ-IFN markedly increased the gene expression and secretion of Clinh. This effect of γ-IFN was abolished by histamine.