A series of patients with fatal progressive systemic sclerosis was reviewed with regard to pathologic, clinical, and serologic evidence of thyroid disease. Histologic evidence of severe fibrosis of the thyroid gland was found significantly more frequently in 56 progressive systemic sclerosis cases (14%) compared to an age and sex matched control autopsy series (2%) from the same institution. Based on determination of serum free thyroxine, free triiodothyroxine (T3), thyroid stimulating hormone, and reverse T3, 27 patients were classified as euthyroid (11), euthyroid sick (9), and hypothyroid (7). Patients with hypothyroidism more frequently had subcutaneous calcinosis, Raynaud's phenomenon, esophageal hypomotility, sclerodactyly, and multiple telangiectasias (the CREST syndrome variant of progressive systemic sclerosis); all thyroid glands from the hypothyroid patients had fibrosis, but lymphocytic infiltration was an infrequent finding. Six hypothyroid patients had high titers of serum antithyroid antibodies, suggesting autoimmune thyroid disease. Thyroid gland fibrosis and hypothyroidism, possibly of autoimmune pathogenesis, are thus frequent and often unsuspected findings in progressive systemic sclerosis.