Pathogenic self-reactive antibodies are a significant cause of morbidlty and mortality and contribute to both cytotoxic and immune complex-trlggered inflammatory dlsorders, typified by rheumatic diseases, autoimmune hemolytic anemia, and thrombocytopenla. Roles have been proposed for Fc receptors, complement, and complement receptors in the pathogenesis of these disorders, although the contribution of each to autoimmune injury is unclear. y chain-deficient mice lacking FcyRl and FcyRlll are resistant to the develop ment of experimental immune hemolytic anemla induced by polyclonal rabbit anti-mouse red blood cell IgG antibodies. Thls resistance Is primarily a consequence of ineffective erythrophagocytosls, resulting from the lack of FcyRs on mononuclear phagocytes. Similarly, y chain-deficient mice are completely resistant to the development of experimental Immune thrombocytopenia induced by mouse anti-platelet antibodies. These data suggest that Fc receptors play an integral role in the pathogenesis of type II hypersensitlvity and suggest potentlal therapeutic beneflts of Fc receptor blockade.