An extracorporeal carbamylation system was evaluated in two patients with sickle cell disease. Access was achieved with existing veins in one patient and an AV fistula in the second. Modifications in the treatment procedure were made as experience indicated. Levels of carbamylation of greater than 1 mol/mol of hemoglobin tetramer were achieved with 4 to 6 hr of treatment every 2 weeks. Cyanate returned to the patient averaged 68.5 mg per treatment. As expected, P50 values decreased and hemoglobin levels increased as the treatment progressed. Patterns of cyanate distribution among the red cell population were those predicted by computer calculations. These observations document the safety and reliability of the treatment system but do not permit conclusions as to efficacy.