Fifty-two episodes of fever, chest pain, increased leukocytosis, and pulmonary infiltrate ("acute chest syndrome") were studied in 28 adults with sickle cell anemia. Possible bacterial pathogens were identified in sputum cultures from less than half of the episodes; no pneumococci were found, and Staphylocococcus aureus was the only bacterium associated with a longer illness than that seen when only normal flora were recovered. Much disease diagnosed as "pneumonia" in adults with sickle cell anemia is probably pulmonary infarction. Many of these patients will recover with no more than modest supportive care; if antibiotics are used they should be directed against S aureus (and possibly Hemophilus species). Pneumococcal polysaccharide vaccine has great potential for preventing life-threatening infection in children with sickle cell anemia, but may not change the incidence or severity of the acute chest syndrome in adults.