Polymorphonuclear (PMN) leukocytes from patients with sickle cell anemia and a history of repeated infection failed to show a stimulation of respiratory CO2, O2 consumption, oxidation of formate and reduction of nitroblue tetrazolium during phagocytosis. The abovementioned abnormalities were not found in PMN leukocytes from patients with sickle cell trait, splenectomized patients and normal individuals. The results of this investigation indicate the presence of an additional predisposing factor to infection in some patients with sickle cell anemia.