An intermittent-flow blood cell separator was used to perform a sub-total RBC exchange pheresis with prompt relief or priapism secondary to sickle cell disease. The blood cell separator offers an efficient, practical, safe method of performing exchange transfusion in the adult. Surgical procedures in the treatment of priapism have met with limited success and carry a 50% rate of subsequent impotence. We believe that RBC exchange pheresis offers a superior approach in the treatment of complications of sickle cell crisis, including priapism, and should be instituted in the symptomatic patient before more drastic procedures are undertaken.