Erythrocyte-bound immunoglobulins have been characterized by a PVP-potentiated antiglobulin test in 11 patients who had developed antibodies after treatment with alpha-methyldopa. Serologic profiles were recognized that could distinguish between the hemolyzing and nonhemolyzing patients: IgM antibodies together with the first component of complement (C1q) were demonstrated on erythrocytes of all eight hemolyzing patients. By contrast, these immunoproteins were absent from the cells of nonhemolyzing patients and became undetectable when the hemolyzing patients recovered. IgG and its subclasses were variably present on erythrocytes of all patients regardless of hemolytic activity. Eluates prepared from erythrocytes of the hemolyzing patients were shown to contain both IgG and IgM, and fixes C1q, C3, and C4. Eluates from the nonhemolyzing patients contained only IgG. The IgM antibodies differed from the commonly occurring cold agglutinins in that they were warm-reactive and were mainly concentrated on the patients' cells rather than being free in the serum. Because of their nonagglutinating property, it is suggested that they are monomeric IgM. It is concluded that the high affinity, warm-reactive IgM and not the IgG antibodies are primarily responsible for clinically manifest anemia in patients receiving alphamethyldopa and that the hemolytic activity is probably mediated by the classic pathway of complement activation.