The existence of hemolysis in sickle cell disease has been documented by both indirect and direct methods. The existence of bone-marrow erythroid hyperplasia, reticulocytosis, indirect hyperbilirubinemia, and elevations of plasma hemoglobin and serum lactic acid dehydrogenase values show hemolytic disease. Direct studies of erythrocyte survival, including the Ashby differential agglutination technique as well as isotopic methods have all shown a markedly decreased red blood cell survival in the range of 10 to 30 days mean cell life-span. Data obtained by means of endogenous production of carbon monoxide have shown that the mean rate of heme catabolism is approximately six times normal but varies from 3 to 14 times normal in individual patients. These data document, by a relatively new technique, the consistent presence of a severe hemolytic process in sickle cell anemia.