The autoimmune disease systemic lupus erythematosus (SLE) is characterized by the deposition of immune complexes in organs such as the kidney. This occurs as a result of multiple immunological abnormalities, including the production of high levels of autoantibody and dysregulated handling of immune complexes. Receptors for the Fc portion of IgG are critically involved in immune complex handling and clearance and in the regulation of B-cell activation. Polymorphisms in the low-affinity Fcgamma receptors have been associated with susceptibility to a number of autoimmune diseases, including SLE. We review the role of two such receptors in the pathogenesis of lupus-the inhibitory receptor FcgammaRIIB and the glycosylphosphatidylinositol-linked activatory receptor FcgammaRIIIB. Recent work has enhanced our understanding of the mechanism of action of the FcgammaRIIB I232T polymorphism and the overall role of this receptor in SLE. The human neutrophil antigen-1 allotypes of FcgammaRIIIB and the role of the receptor in SLE are discussed with regard to the recent determination of copy number variation in FCGR3B and the association of low copy number with SLE.