Bacterial septicemia and meningitis are major causes of death in young children with sickle cell anemia. We report a prospective study of 182 episodes of fever among 22 children with sickle cell diseases identified at birth. The majority of patients with fever exceeding 39.5 degrees C were treated with antibiotics intravenously until results of blood cultures were known. Infectious diseases were documented in 38% of all febrile events. Six episodes of bacterial septicemia, two associated with meningitis, were successfully treated with no mortality or residual morbidity. These data form the basis of suggestions for management of the young child with sickle cell disease and fever.