The course of acute noninfectious pulmonary infiltrates in five patients with myeloblastic leukemia was evaluated. All had circulating blast cells (range, 245-192,000/mm3) and recently had received chemotherapeutic drugs for their leukemia. Within four days of the nadir of their leukocyte counts, a patchy, often multilobar pneumonitis developed. Cultures for bacteria, fungi, and viruses were all negative, and no clinical response was observed to broad-spectrum antibiotics. On lung biopsy, pathologic changes were characterized by diffuse alveolar damage with degenerating blast cells in the interstitium and in organizing alveolar exudates. No potential pathogenic organisms were seen on light or electron microscopy of the biopsy samples. In each case the pulmonary infiltrate resolved without specific therapy. We postulate that lysis of leukemic cells, with subsequent release of their enzyme contents, led to the diffuse alveolar damage observed pathologically. Leukemic cell lysis pneumonopathy may be one of the potential causes of pulmonary infiltrates in leukemic patients and can be distinguished pathologically by its distinctive pattern.