Patients with sickle cell disease are commonly hospitalized for acute, febrile pulmonary episodes that in children are generally due to severe infection. Vascular occlusion and infarction are more common in older age groups and may coexist with infection. Pneumococci are frequently the responsible infectious agent. Overwhelming bloodstream invasion and meningitis may occur due to impaired function of the spleen, the serum properdin system, and of neutrophils. Prophylaxis with penicillin has been advocated and immunization with polyvalent pneumococcal capsular vaccines is under study. Pulmonary infection and vascular occlusion with infarction are difficult to differentiate. The probably nonthromboembolic nature of the vascular occlusive process and the increased incidence of serious bleeding in sickle cell disease make anticoagulation or fibrinolytic therapy of dubious value. In some patients, widespread pulmonary vascular occlusion produces chronic pulmonary hypertension and cor pulmonale.