Eleven days after administration of multiple penicillin analogs, a 55-year-old female developed a Coombs-positive hemolytic anemia. The patient's erythrocytes were coated with IgG, complement components (C4/C3) and her serum contained elevated 125I-Clq binding activity (a measure of the presence of immune complexes). Her serum, in the presence of fresh complement and penicillin, induced complement sensitization of normal erythrocytes. Immune complex-mediated complement activation and the haptene type of erythrocyte sensitization accounted for accelerated red blood cell destruction in this patient.