Complement components, particularly C3, are known to be involved in the pathogenesis of AIDS and macrophages may serve as a source of C3 at sites of infection. We investigated whether the interaction between HIV-1 and monocytes has any effect on C3 production by the cells. Monocytes isolated from the blood of healthy volunteers were incubated with monocytotropic and T lymphocytotropic HIV-1 strains or with recombinant gp160 and cultured in serum-free medium up to 7 days. Supernatants were tested for secreted C3 by enzyme-linked immunosorbent assay. Our data show that monocytes cultured with either the monocytotropic or the T lymphocytotropic HIV-1 strains produce C3 in large amounts. The effect of both viruses is dose dependent and the amount of C3 induced by HIV was up to 20-fold higher than in the control samples. C3 production was also enhanced by gp160, the envelope protein of the virus. Secretion of IL-6 by the cells was also measured and found to be elevated up to threefold as a consequence of the interaction with the virus. HIV-1-activated monocyte-derived macrophages acquired the capacity to cleave exogenous C3 and to fix generated C3 fragments on their cell membrane.