Most patients with adult respiratory distress syndrome (ARDS) survive the initial insult which caused respiratory failure only to succumb later to sepsis caused by nosocomial pneumonia or to pulmonary fibrosis. Clinical criteria and analysis of the tracheal aspirate are notoriously inadequate for establishing a diagnosis of ventilator-associated pneumonia. We implemented a comprehensive diagnostic protocol to determine the cause of sepsis in ARDS patients who had been ventilated for more than three days and who had no bronchoscopic evidence of pneumonia. Nine patients with late ARDS who had fever (89 percent), leukocytosis (89 percent), a new localized infiltrate (78 percent), purulent tracheal secretions (89 percent), low systemic vascular resistance (50 percent), and marked uptake of gallium in the lungs (100 percent) had no source of infection identified. Open-lung biopsy specimens from seven patients showed the fibroproliferative phase of diffuse alveolar damage and confirmed absence of pneumonia. Treatment with prolonged high doses of corticosteroids was associated with a marked and rapid improvement in lung injury score (p less than 0.003 at five days). Our findings indicate that the fibroproliferative process occurring in the lungs of patients with late ARDS gives rise to clinical manifestations identical to those of pneumonia and is potentially responsive to steroid treatment.