A patient with sickle cell disease (hematocrit, 28.5%; hemoglobin S fraction, 79%), required mitral valve repair. Partial red cell removal and blood component sequestration with an autotransfusion device before cardiopulmonary bypass initially decreased the sickle red cell mass. This was followed by an acute one-volume whole blood exchange transfusion performed upon the initiation of cardiopulmonary bypass, resulting in a further reduction. Both techniques yielded fresh autologous plasma for use; sequestration yielded a platelet-pheresis product. Adequate postbypass hemostasis was demonstrated.