The clinical charts and histologic preparations from 245 patients who had pleural biopsies to evaluate pleural effusions of unknown etiology were reviewed. This represents an experience with 272 biopsies, as some patients underwent multiple biopsies. In 57 per cent of the cases of suspected or proven granulomatous disease involving the pleura, the pleural biopsy was positive. Similarly, in 48 per cent of the cases of suspected or proven pleural involvement by carcinoma, tumor was identified in the biopsy specimen. Only two false-positive diagnoses (one of granulomatous pleuritis and one of neoplastic disease) were made. The other 35 histologic diagnoses of granulomatous inflammation and 43 histologic diagnoses of carcinoma were verified. In this study, the authors found that the major limiting factor in establishing a diagnosis is the accuracy in random sampling of the parietal pleural surface. Thus, a negative pleural biopsy should not give the clinician a false sense of security.