Mixed connective tissue disease (MCTD) has been characterized as a benign rheumatic syndrome with a favorable response to immunosuppressive therapy. Serious renal and pulmonary involvement are reported to be rare in MCTD. We are describing a female adolescent with MCTD in whom fatal cor pulmonale developed due to recurrent thromboembolic primary pulmonary hypertension. Death occurred after two years of therapy with prednisone and azathioprine for an immune-complex glomerulonephritis. Paramesangial and intramembranous electron-dense deposits had been identified in several glomeruli at the start of treatment. Improved renal function and apparent histologic improvement were demonstrated four months after the institution of prednisone and azathioprine therapy, and stable renal function was maintained until death. The pulmonary hypertension was progressive and apparently not altered by either the prednisone or azathioprine. At necropsy, there was no evidence of a pulmonary arteritis or vascular immune-complex deposition to account for the recurrent thromboembolic lesions in the small pulmonary arteries and arterioles. This is a clinical course not previously described in patients with MCTD and may represent an extreme of the clinical spectrum of this syndrome.