Patients with diffuse pulmonary infiltrates and acute respiratory failure (ARF) potentially can benefit from diagnostic information provided by open lung biopsy (OLB). To better quantify possible benefits and risks, we reviewed an 11-yr experience with 80 such patients. Although OLB did provide a specific etiologic diagnosis in 53 patients (66%) and did influence therapy in 56 patients (70%), only 24 patients (30%) survived to hospital discharge, and 9 patients (11%) survived for 1 yr or more. Survival rates did not depend on the availability of a specific diagnosis, changes in diagnosis, or changes in therapy. Survival was improved in younger patients and patients not requiring preoperative mechanical ventilation. Fifteen patients (19%) suffered complications possibly related to OLB; the survival rate to discharge was decreased in these patients, although not significantly. We conclude that OLB provides a specific etiologic diagnosis in many patients with diffuse pulmonary infiltrates and ARF, but that its utility in these patients is limited by current shortcomings of therapy.