Eighteen patients with sickle-cell disease underwent partial exchange transfusion. Three developed delayed hemolytic reactions, with selective disappearance of transfused cells. All reactions occurred within 6 days of transfusion, and patients presented with the clinical features of painful crises. The two most severe reactions were associated with antibodies to Jk(a). These patients developed fever, arthritis, and a clinical course suggesting serum sickness. In both patients, other alloantibodies had previously been seen. A fourth patient developed multiple alloantibodies, accelerated destruction of transfused cells, but milder illness. Such reactions may be commoner than is appreciated and should be suspected when patients have recurrent or severe sickle crises after transfusion. Blood that is nonimmunogenic in antigen systems frequently associated with delayed hemolytic reactions (Rh, Kell, Duffy, and Kidd) is preferred for sickle-cell patients who lack these antigens, especially if these patients have previously demonstrated capability to form erythrocyte alloantibodies.