Abnormalities in host mechanisms for the handling of immune complexes (IC) may promote both tissue deposition of pathogenic complexes and interaction of complexes with other immunocompetent cells. Although immune adherence of complexes to erythrocytes may be decreased in patients with autoimmune disease, the significance of this decrease for overall immune complex handling is unclear since many IC release rapidly from the erythrocytes. Little is known about the role of complement receptors in IC uptake by phagocytes. . In contrast, the observations of defective Fcγ receptor-mediated uptake of IgG ligand-coated erythrocytes (one model for erythrocyte-bound complexes) by fixed tissue macrophages in SLE patients demonstrate the role of Fcγ receptors in the uptake of these complexes. Although partly acquired and related to disease activity in SLE, the Fc-mediated clearance defect may also have a genetic component. Inherited differences in Fcγ function may reflect structural polymorphisms of the involved Fc receptors. The emerging picture of Fcγ receptor structural diversity - several different receptor families (FcγRI, FcγRII, and FCγRIII) each with different isoforms, the potential for different glycoforms and cell anchoring mechanisms, and allelic variations within the isoforms-provides the basis for structure/function relationships which have clear implications for autoimmune diseases with abnormal Fc receptor function.