We have previously reported that FcγR-mediated function in myeloid cells is a tightly regulated event that is influenced by the cytokines present in the milieu. TGF-β1 is an immunosuppressive cytokine with pleiotropic effects on immune responses; however, the molecular mechanism by which TGF-β suppresses immune responses is poorly understood. In this study, we have analyzed the effect of TGF-β on FcγR-mediated activation of myeloid cells. We report that TGF-β1-treated THP-1 human myeloid cells displayed reduced ability to phagocytose IgG-coated particles. Because FcγR expression is modulated by cytokines, we analyzed expression levels of FcγRI, FcγRIIa, FcγRIIb, and FcγRIIIa in cells cultured with or without TGF-β1 and found while total protein levels of the FcγR were not reduced, surface expression of FcγRI and FcγRIII was lower in cells cultured with TGF-β1. Concomitantly, there was a dose-dependent reduction in the expression of the FcγR-associated γ-subunit. This suppressive effect of TGF-β was likewise observed in bone marrow-derived murine myeloid cells and human monocytes. Importantly, TGF-β1 also significantly reduced the production of monocyte chemoattractant protein-1 induced by immobilized IgG, which would further reduce monocyte recruitment to the site of inflammation. In contrast, human alveolar macrophages were refractory to this effect, expressing low levels of TGF-β type II receptors compared with peripheral blood monocytes from the same donor. These data provide insight into the regulation of immune responses by TGF-β1 and demonstrate the selectivity of these effects.