Clearance of immune complexes by the mononuclear phagocyte system is important for maintaining normal host defenses against bacterial and viral assault (1), but also contributes to the pathogenesis of a variety of immune-mediated diseases . For example, removal from the circulation of IgG-coated erythrocytes and platelets by the MPS is the sine qua non of immune-mediated cytopenias (2, 3). On the other hand, abnormally decreased removal by the MPS of smaller, soluble immune complexes may play a role in the pathogenesis of immune complex-mediated tissue damage found in such autoimmune diseases as SLE (4).Although the physicochemical nature and the size of immune complexes can influence rates of clearance and sites of deposition (reviewed in 5), interactions between immune complexes and the MPS in vivo are poorly understood . The inability to directly measure binding or internalization of immune complexes by cells in the liver and spleen has made the analysis of the molecular basis of immune complex clearance very difficult . Receptors for the Fc portion of IgG (FcyR) and for complement (CR) undoubtedly play a role in the removal of immune complexes, but the relative importance of these receptors is not known.There are three types of FcyRs on human leukocytes . A 72 kD receptor with high affinity for monomeric IgG is found on monocytes (6) and some resident macrophages (7). Two receptors exist with low affinity for monomeric IgG, one with broad electrophoretic mobility (51-73 kD) on neutrophils (8), natural killer cells (9), and macrophages (8); the other recently described (40 kD) on platelets (10), monocytes (10), and several tumor cell lines (11). All three bind immunoglobulin that is aggregated or complexed to antigen . The 51-73 kD receptor is recognized by mAb 3G8, which blocks ligand binding and has been very useful in the partial biochemical characterization of this receptor (8).In vitro analysis of the role played by FcyRs in individuals with abnormally prolonged clearance of opsonized red cells (model particulate immune complexes) generally has been limited to studies of high-affinity FcyRs on monocytes.