Carbon monoxide at a concentration of 1000-2000 ppm was administered to sickle cell disease patients. In each of two patients, one 51Cr red cell survival study was carried out before CO administration, and a second study was initiated a few days before CO administration was started. In both, significant prolongation of red cell survival was observed, suggesting that the rheologic properties of sickle cells were favorably influenced in vivo. The administration of carbon monoxide is not recommended as a treatment for sickle cell disease. However, further trials would seem to be justified if conducted under carefully controlled conditions.