A 21-year-old white worn was referred for evaluation of hemolytic anemia after a 9-day history of marked hemoglobinuria, jaundice, and weakness. The patient's hematocrit was 18%, despite at least eight transfusions over the previous week, and the reticulocyte count was < 1%. Serologic evaluation revealed a weakly positive direct antiglobulin test with anti-C3 only The serum contained cold and warm-reacting anti-N Dithiothreitol had no effect on either the cold- or the warm-reacting anti-N activity, and radioimmunoassay with monoclonal anti-IgG was strongly positive, indicating that both the cold- and the warm-reacting anti-N reactivity resided in the IgG fraction. The patient was treated with N - 'N' + red cell transfusions, prednisone, and azathioprine and gradually became transfusion independent. Postrecovery typing revealed her red cells to be M+N+S+s+. This constitutes the third case of autoimmune hemolytic anemia associated with IgG autoanti-N. The marked hemoglobinuria and reticulocytopenia are unique features of this case.