The Bio Breeding/Worcester (BB/W) rat develops spontaneous insulin-dependent diabetes mellitus secondary to lymphocytic infiltration and destruction of the pancreatic beta-cells. This destructive process in the pancreas has been postulated to be based on a thymus-dependent cell-mediated autoimmune process. In view of the well recognized association in man of diabetes mellitus and another autoimmune endocrinopathy, chronic thyroiditis (Hashimoto's thyroiditis), the present studies were carried out to determine whether lymphocytic thyroiditis occurred with increased frequency in the diabetic, insulin-treated BB/W rat. The incidence of lymphocytic thyroiditis was strikingly increased in 8-10-mo-old diabetic rats (59%) as compared with their nondiabetic cohorts (11%) (P less than 0.001). Relative thyroid weight was significantly greater in diabetic as compared with nondiabetic rats (P less than 0.01) and in diabetic rats with thyroiditis than in diabetic rats without thyroiditis (P less than 0.025). Lymphocytic thyroiditis was not accompanied by any consistent changes in serum T4, T3, and TSH concentrations or in the serum TSH response to thyrotropin-releasing hormone (TRH) suggesting that the thyroiditis was not of sufficient severity or duration to induce primary thyroid gland failure. The BB/W rat represents the first animal model of multiple autoimmune endocrinopathies and provides a unique opportunity to study the pathogenesis of these disorders.