A 71-year-old male with severe autoimmune hemolysis with both cold agglutinins and warm antibodies was intolerant of prednisone and cyclophosphamide. Rituximab was given during a 60-day period when he required 41 units of packed cells to maintain hemoglobin above 75 g/l. Two weeks later hemoglobin stabilized at 95 g/l, and further transfusions were not required. A second course of rituximab was given 4 months later for continued hemolysis. A satisfactory hemoglobin was maintained for 9 months from initial treatment, when hemoglobin again fell to 65 g/L. A prompt response to a third course of rituximab was obtained. This is the second patient with both cold agglutinins and warm antibodies with severe hemolytic anemia who has had a prompt response to rituximab. This treatment should be considered when a rapid response is needed or when a patient has failed to respond to more standard therapies.