Red cell distribution width (RDW), an electronically determined index of anisocytosis, was examined in 60 patients with sickle cell anemia (Hb SS), 28 patients with hemoglobin sickle cell (SC) disease, and seven patients with sickle cell-beta(+) thalassemia (S-thal). All patients were adults and in the steady state of their disease. The RDW was greater in sickle cell patients than in 39 healthy, age and race matched controls without hemoglobinopathy (Hb AA). Patients with sickle cell anemia had higher mean RDW than those with Hb SC disease or with S-thal. The mean RDWs in the latter two disorders were not significantly different. In SS patients, the RDW correlated significantly with the degree of anemia and reticulocytosis. A group of 18 SS patients was studied while in acute painful crisis. Their mean RDW was not different from that in the steady state. Mean WBC and red cell volume, however, were significantly higher during pain crisis.