Pulmonary involvement in mixed connective tissue disease has been considered a benign manifestation that is easily treated with corticosteroids. We followed 5 patients who had mixed connective tissue disease and severe, rapidly progressive, lung disease. Two types of lung disease were found, interstitial lung disease and pulmonary hypertension. Histologic sections from our patients were compared with sections from patients who had interstitial lung disease and systemic lupus erythematosus or pulmonary hypertension and scleroderma. Although clinical presentations were similar, the immunofluorescent and electron microscopic findings for interstitial lung disease were somewhat different in patients with systemic lupus erythematosus. Histologic findings for pulmonary hypertension appeared different in patients with mixed connective tissue disease and patients with scleroderma. For patients with either type of lung disease, corticosteroid therapy proved inadequate, but nearly cytotoxic therapy may be beneficial.