The effects of lα,25-dihydroxyvitamin D₃/caldtriol on the expression of Fc receptors (FcR) for IgA (FcαR), IgE (FcRII), and IgG (FcγR) on human peripheral blood monocytes and the cell lines U937, THP-1, and Mono Mac-6, in combination with various cytoldnes, was examined by flow cytometry. On both monocyte-derived macrophages and the myelomonocytic cell lines, FcαR/CD89 expression was induced by caldtriol alone and additively in combination with tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and granulocyte-macrophage colony-stimulating factor. Constitutive and mterleukin-4 (IL-4)-driven FcRD/CD23 expression was markedly diminished on caldtriol-treated U937 cells and monocytes. FcRII was also triggered by IFN-γ, TNF-α, and IL-6 on all the cell lines, an effect blocked by caldtriol. On monocytes, the basal level and IFN-γ-induced FcγRI/CD64 expression was down-regulated by caldtriol and IL-4. The expression of FcγRII/CD32 on monocytes was strongly suppressed by caldtriol. Transforming growth factor-β induced FcγRIII/CD16 on monocytes, an effect opposed by caldtriol. The ability of caldtriol-treated monocytes to phagocytose IgG-sensitized ox erythrocytes was diminished. Our results demonstrate that caldtriol, alone or in combination with cytokines, modulates FcαR, FcRII, FcγRI, and FcγRII expression on human mononudear phagocytes, as well as FcγR-mediated phagocytosis. J. Leukoc. Biol. 58: 256–262; 1995.