Bronchiolitis obliterans with organizing pneumonia (BOOP) is a distinct clinical pathologic syndrome. Most patients experience a good response to therapy, and death from progressive BOOP is uncommon. This report describes the clinical features, etiologic factors, pathologic findings, and outcome of 10 patients with rapidly progressive BOOP that was characterized by severe respiratory failure. The major clinical manifestations were dyspnea, cough, fever, crackles on chest examination, and hypoxemia at rest. Underlying conditions or exposures included connective-tissue disease, exposure to birds, and chronic nitrofurantoin therapy. All patients had the characteristic histopathologic findings of BOOP. However, at autopsy in six patients, the predominant histologic pattern was that of alveolar septal inflammation and fibrotic honeycombing. Seven patients died and three patients survived but had persistent pulmonary dysfunction despite aggressive care. In two patients BOOP has progressed, with severe chronic respiratory decompensation. Thus, there is a subset of patients with BOOP who present with a fulminant course leading to death or chronic severe fibrosis and marked impairment of lung function. In addition, the histologic picture of BOOP may be a manifestation of early lung injury that can resolve or progress rapidly to alveolar septal inflammation, end-stage fibrosis, and honeycombing.