Partial exchange transfusion is used to manage several of the complications of sickle cell anemia. Automated exchanges have been performed successfully in thirteen homozygous (SS) sickle cell patients and in one patient with hemoglobin SC. Although the expected acute increase in whole blood oxygen affinity occurred in each patient, there was no clinical evidence of detrimental effects during or immediately after each procedure, and in each case the patient was unchanged or improved when evaluated by exercise testing. By using a discontinuous-flow cell separator, it is possible to decrease the time required to achieve a 50 per cent exchange in an adult to approximately two hours. Transfusion of blood with an antigenic marker permits rapid evaluation of exchange efficiency during the procedure. When partial exchange transfusion is indicated, the discontinuous-flow cell separator provides a safe, rapid, and effective procedure.