Receptors for the Fc portion of immunoglobulin molecules (FcR) present on leukocyte cell membranes mediate a large number of cellular responses that are very important in host defense. Cross-linking of FcR by immune complexes leads to functions such as phagocytosis, cell cytotoxicity, production and secretion of inflammatory mediators, and modulation of the immune response. Molecular characterization of FcRs indicates the existence of several types of these receptors, which seem to be redundant in their cell distribution and function. There is a great deal of interest in understanding how these various receptors signal the cell to respond in different ways during inflammation and the immune response. Previous studies indicate that FcR signaling shares elements with the T and B cell antigen receptors. Signaling is initiated in all of them by activation of tyrosine kinases of the Src and ZAP-70 families. Subsequent events, which vary depending on the cell type and receptor involved, include activation of other enzymes such as phospholipase Cgamma1, phosphatidylinositol-3-kinase, and mitogen-activated protein kinase. Several recent lines of research, including studies of phagocytosis by FcR-transfected cells, antibody-dependent cytotoxicity by natural killer cells, mast cell degranulation, and FcR-deficient mice, have given us new insights on the signal transduction pathways activated by FcRs. This review describes the advances in these areas and presents a general model for FcR-mediated signaling.