ABSTRACTAlthough much is known about the hematologic and pathophysiologic aspects of autoimmune hemolytic anemia in man, the pathogenesis of the autoimmune process remains to be elucidated. Toward this goal, several experimental animal models, in particular the New Zealand black mouse, have been extremely important in laying the foundations of our present knowledge of the pathogenesis of the autoimmune process. The interaction of environmental, genetic, and immunologic factors plays an important role in the clinical manifestations of the hemolytic disease and the eventual outcome of the autoimmune process. The increased frequency of autoimmune disorders in patients with primary immunodeficiency disorders emphasizes the importance of disturbances of immunoregulation and immune dysfunction in the pathogenesis of autoimmune hemolytic disease.