Many of the findings ascribed to autoimmunity on the basis of experimental studies could be due to isoimmunity. By this is meant an antibody to an antigenic determinant which is present in some members of a species but not in the particular individual in whom the antibody is detected. The Ag system involves inherited antigenic specificities on the low density lipoproteins. Antibodies against these determinants may form in patients who receive many transfusions or in pregnant women. The role of these antibodies in disease is discussed. The Australia antigen is intimately associated with what appears to be an infectious agent which causes hepatitis in some people infected with it. In addition, it has many features of a serum polymorphism, and isoantibodies may form against it in people infected by transfusion or other means. The relation of these two systems to “autoimmune” phenomena is discussed.