Biochemical studies reveal that erythrocyte blood group antigens are the immunological expression of polymorphic and, frequently, biologically-active membrane structures. Some of these structures have been identified to be specific transport proteins, enzymes, or receptors for infectious agents. Certain erythrocyte phenotypes, for example, Rh(null), lack all or most antigens in a specific blood group system. Changes in erythrocyte morphology and function associated with these phenotypes provide insights into the roles of the corresponding proteins in the maintenance of membrane integrity. Other phenotypes, for example Oh, and p, also lack multiple blood group antigens, but the absence of changes in morphology or function in these erythrocytes suggests that their corresponding carbohydrate determinants are not essential for maintaining membrane integrity. Additional information on the function of erythrocyte membrane structures that express blood group antigens is likely to advance our understanding of the role of blood groups in health and disease.