Fc receptors (FcR) for IgG on human cells were analyzed with two monoclonal antibodies, 3G8 and 4F7. Fab fragments of both hybridoma IgGs inhibited binding to neutrophils of soluble rabbit IgG complexes and sheep erythrocytes (E) coated with rabbit IgG. The number of sites for 3G8 Fab was 135,000 per neutrophil, roughly equivalent to the number of sites for rabbit IgG in immune complexes (112,000 per cell). We did not observe human IgG1 binding sites on neutrophils, although binding of IgG1 to FcR-bearing lines U937 and HL-60 was readily demonstrated. Other cell types bearing 3G8 binding sites were mature chronic myelogenous leukemia cells, eosinophils, 6% of E-rosetting lymphocytes, and 15% of Ig-bearing peripheral lymphocytes. No binding of 3G8 Fab was observed on the FcR-bearing cell lines U937, HL-60 Raji, Daudi, and K562 or on blood monocytes. However, 15% of monocytes cultured for 7 days and 60% of lung macrophages expressed 3G8 antigen. When analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis, the neutrophil FcR immunoprecipitated with 3G8 or 4F7 Fab-Sepharose displayed a broad band extending from Mr 73,000 to 51,000; in many experiments this band was resolved into two poorly separated components, centered at Mr 66,000 and 53,000. These results show that human neutrophil FcR for IgG is different from that on monocytes, with respect to both antigenic composition and binding of monomeric IgG1.