The effects of extracorporeal carbamylation were determined in four patients with sickle cell anemia. Treatments were carried out in clusters every 4 to 6 weeks over a 6-month period. Mean carbamylation achieved in vivo was 1.3 moles cyanate per mole of hemoglobin. The mean in vitro P50 during treatment was 22.1 mm. Hg as compared to the pretreatment value of 30 mm. Hg. Hemoglobin concentration was increased over the 6 months by 24 per cent. The treatment resulted in the stimulation of erythropoiesis. Treated cells had a prolonged survival of about 40 days, but bilirubin did not fall. Blood volume and heart size remained unchanged. Carbamylation did not appear to alter the degree of sickling at any given O2 saturation. Painful attacks continued through the treatment period with a frequency of 84 per cent and a severity-frequency index of 77 per cent of that in the control period. There was no evidence of cyanate toxicity associated with extracorporeal therapy.