A high frequency of occurrence of pleuropulmonary manifestations in mixed connective tissue disease (MCTD) has been reported in the literature. A retrospective analysis of 81 adult patients with the diagnosis of MCTD who were examined at our medical center from 1973 through 1977 revealed that pleuropulmonary involvement occurred in 20 (25%). Thirteen patients (16%) had dyspnea, six (7%) had chest pain, and four (5%) had cough. Chest roentgenograms disclosed basal interstitial processes in 15 patients (19%), pleural effusion in 5 (6%), pneumonic infiltrates in 3 (4%), and pleural thickening in 2 (2%). Abnormalities of pulmonary function were noted in 9 (69%) of 13 patients tested, and esophagographic abnormalities were present in 19 (53%) of 36 patients tested. Systemic corticosteroid therapy was beneficial in two of the eight patients so treated, and nonsteroidal anti-inflammatory drugs resolved most of the clinical features in four of the seven patients so treated. Six patients died during a 5-year follow-up period.