Five hundred patients with pulmonary disease underwent diagnostic techniques not involving thoracotomy. The biopsies taken were by cutting needle, trephine, bronchial brush, and bronchofiberscope. Mediastinoscopy, anterior mediastinotomy and thoracoscopy were employed as supplementary procedures. The diagnostic accuracy was between 70% and 90%. One or a combination of methods was found highly valuable in patients who were inoperable with bronchogenic carcinoma, critically ill, immunosuppressed, or aged. Postbiopsy complications were not serious except for cutting needle biopsy in diffuse parenchymal disease, where a 31% incidence of bleeding was encountered. In localized pulmonary disease, fiberoptic bronchoscopy with brush biopsy was the best initial approach, especially if the lesion was located centrally enough for endoscopic visualization. In diffuse disease, trephine biopsy was the best percutaneous technique for obtaining a piece of lung tissue.