Video-assisted thoracic surgical lung biopsy is an alternative to traditional open lung biopsy for diagnosis in patients with pleuropulmonary diseases. Between January 7, 1991, and August 3, 1993, 71 consecutive patients had video-assisted thoracic surgical lung biopsy and 42 patients had traditional open lung biopsy. A specific histologic diagnosis that correlated with the clinical findings was sought in each case and the yield was compared between the two groups. Procedure-related artifactual changes were also evaluated; the extent of traumatic hemorrhage and neutrophil margination as a result of tissue manipulation was significantly greater for patients in the video-assisted thoracic surgical lung biopsy group than for those in the open lung biopsy group, but the changes were generally minor and did not affect diagnostic yield. Complications developed in 11 (15%) of 71 patients in the video-assisted thoracic surgical lung biopsy group including 5 patients with prolonged air leakage (more than 10 days); 2 with pneumonia; and 1 each with bleeding, late pneumothorax necessitating readmission, mucus plug necessitating bronchoscopy, and a hypoxic episode necessitating mechanical ventilation. On the other hand, 7 (17%) of 42 patients in the open lung biopsy group had complications including 4 patients with prolonged air leakage (more than 10 days) and 3 with pneumonia. There were 6 (8%) operative deaths in patients who had video-assisted thoracic surgical lung biopsy and 7 (17%) in the open lung biopsy group; all had preoperative respiratory failure. We conclude that video-assisted thoracic surgical lung biopsy is an acceptable alternative to open lung biopsy for diagnosis of pulmonary infiltrates or indeterminate nodules.