Over a 4-year period, 25 patients with pulmonary complications of acquired immunodeficiency syndrome underwent open lung biopsy for diagnosis. Results of the biopsy led to a change in therapy in 15, and of this group, 8 patients improved clinically and were discharged. We believe that a select group of acquired immunodeficiency syndrome patients with pulmonary disease will benefit from open lung biopsy. Our indications for open lung biopsy are (1) a nondiagnostic bronchoscopy, (2) failed medical therapy after a diagnostic bronchoscopy, (3) failed empiric medical therapy after a nondiagnostic bronchoscopy or after a second nondiagnostic bronchoscopy, and (4) when any of the forementioned are accompanied with a worsening chest roentgenogram. Patients with acquired immunodeficiency syndrome who have a deteriorating respiratory status or require mechanical ventilation should not undergo open lung biopsy.