Four patients with acute nonlymphocytic leukemia and leukocyte counts of more than 200,000/mm3 developed respiratory distress due to pulmonary leukostasis within 10-48 hours after initiation of chemotherapy. Clinically, the patients manifested fever, dyspnea, tachypnea, diffuse pulmonary rales, pleural effusions, and severe hypoxemia. Chest roentgenograms displayed diffuse pulmonary infiltrates, vascular engorgement, cardiomegaly, and pleural effusions. Three patients died from progressive respiratory failure despite ventilatory support. Pulmonary histology revealed thrombi composed of leukemic blast cells which obstructed and distended the lumens of pulmonary arterioles, capillaries, and venules. Electron microscopy studies of lung tissue showed pulmonary alveolar endothelium and basement membrane damage and interstitial edema. The pathophysiologic basis of pulmonary leukostasis and potential treatment modalities are discussed.