We examined expression and cytotoxic triggering capability of the three Fc receptors for IgG (Fcγ R) on human monocytes, PMNs and myeloid cell lines after in vitro culture with various cytokines. Fcγ R expression was evaluated using specific anti-Fcγ R monoclonal antibodies (mAb). The cytotoxic capability of each Fcγ R was examined after the effector cells were treated with the recombinant cytokines IFN-γ, TNFα, GM-CSF, G-CSF, M-CSF, IL-1, IL-2, IL-3, IL-4, or IL-6. Hybridoma cell lines (HC) bearing antibody directed to FcγRI (HC 32), FcyRII (HC IV.3) or FcyRIII (HC 3G8) were used as targets, as were chicken erythrocytes (CE) sensitized with heteroantibodies composed of anti-Fcy R mAbs (32, IV.3, 3G8) linked to anti-CE antibody. Only IFN-γ treatment significantly increased FcγR expression and then only FcγRI. IFN-γ dramatically up-regulated FcγRI expression on all cells tested. However, ADCC was enhanced by treatment with a number of cytokines other than IFN-γ. GM-CSF, TNF, and IFN-γ treatment enhanced killing of HC 32 and HC IV.3 by in vitro cultured monocytes. G-CSF treatment enabled PMNs to kill HC through Fcγ RII, whereas PMN killing of HC through FcγRIII could not be induced by any of the cytokines studied. Although only IFN-γ treatment increased ADCC of CE by monocytes, GM-CSF treatment as well as IFN-γ treatment augmented ADCC of CE by PMNs. In addition to IFN-γ treatment, IL-6 treatment enabled U937 cells to lyse CE. Whereas IFN-γ-treated U937 cells killed CE through both FcyRI and FcyRII, IL-6-treated U937 cells killed CE only through Fcγ RI. In addition to IFN-γ treatment, G-CSF treatment enabled HL-60 cells to lyse CE through both FcyRI and Fcγ RII. These results demonstrate that although IFN-γ appears unique in regulating Fcγ R expression on myeloid cells, cytokines other than IFN-γ affect ADCC by these cells in a receptor-specific manner.