The value and risk of transbronchial biopsy (TBB) was assessed in 15 cases requiring mechanical ventilation for progressive pulmonary infiltrates. TBB was diagnostic in five patients, and in two additional cases a diagnosis was made from the accompanying bronchial secretions. TBB results significantly altered the therapeutic management in seven cases. The alveolar-arterial gradient P(A-a)O2, widened by a mean of 110 mm Hg in nine patients; however, this change was transient and clinically insignificant. Three instances of reversible hypercapnia (mean of 15 mm Hg) occurred. Complications included self-limited bleeding in three cases and one tension pneumothorax. No fatalities were attributable to TBB. In these hemodynamically stable patients requiring mechanical ventilation for diffuse lung disease, TBB was performed safely and provided important data.