In a 17-month period, 20 immunosuppressed patients underwent transbronchial biopsy of the lung for diagnostic evaluation of a pulmonary infiltrate of unknown etiology. In 19 patients, the transbronchial biopsy was nondiagnostic. Thirteen of the 19 patients were critically ill and were referred for an open lung biopsy. Eleven (85 percent) of these 13 patients left the hospital after open lung biopsy and appropriate medical treatment. Two patients who were receiving mechanical ventilation at the time of open biopsy succumbed to the combination of their underlying disease and respiratory failure. There were no deaths directly attributed to the open lung biopsy. Of the six patients whose condition appeared stable and who did not undergo open lung biopsy, two died from unrecognized progress of their underlying malignant disease. The remainder recovered. We conclude that open lung biopsy is safe in and beneficial to the diagnosis and subsequent treatment of unknown pulmonary infiltrates in immunosuppressed patients who previously had a nondiagnostic fiberoptic transbronchial biopsy of the lung.