The term mixed connective tissue disease is used to identify the patients with combined clinical features of systemic lupus erythematosus, scleroderma or progressive systemic sclerosis, and polymyositis-dermatomyositis. A prerequisite for the diagnosis of mixed connective tissue disease is the presence, in the serum, of high titers of antibodies against uridine-rich RNA-small nuclear ribonucleoprotein (snRNP). Respiratory and nonrespiratory features of the disease follow those seen in systemic lupus erythematosus, scleroderma, or progressive systemic sclerosis, and polymyositis-dermatomyositis. Respiratory involvement is observed in 20% to 80% of patients. Major respiratory manifestations and their incidences described include interstitial pneumonitis and fibrosis (20% to 65%), pleural effusion (50%), pleurisy (20%), and pulmonary hypertension (10% to 45%). Other pulmonary features consist of pulmonary vasculitis, pulmonary thromboembolism, aspiration pneumonia, pulmonary hemorrhage, pulmonary nodules, pulmonary cysts, obstructive airways disease, mediastinal lymphadenopathy, pulmonary infections, hypoventilatory respiratory failure, and diaphragmatic dysfunction. Pulmonary hypertension is a serious complication; rapid deterioration and death have occurred in spite of corticosteroid and cytotoxic chemotherapy.