Oral tolerization with the appropriate antigen(s) to ameliorate autoimmune diseases in humans and in experimentally induced animal models, including experimentally autoimmune thyroiditis in mice, has been reported to be efficacious. Spontaneous and iodine induced (0.05% iodine in the drinking water) lymphocytic thyroiditis (LT) occurs in the diabetes mellitus (DM)-prone BioBreeding/Worcester (BB/Wor) rat. The present study was carried out to determine whether the oral administration of human thyroglobulin (hTg) would decrease the incidence of spontaneous and iodine-induced LT in the BB/Wor rat. Low iodine content hTg or bovine serum albumin (BSA) were given orally every 2 days for six doses beginning at age 50 days to BB/W rats, half of whom also received iodine in their drinking water. No effect or orally administered hTg was observed on thyroid weight, the incidence of LT or DM, or on serum thyroglobin antibodies (TgAb), thyrotropin (TSH), thyroxine (T4), and triiodothyronine (T3) concentrations when rats were killed at 100 days of age. In a second experiment, the oral administration of iodine rich hTg or BSA every 2 days for six doses beginning at 30 days of age to iodine-treated BB/Wor rats again did not affect the high incidence of LT or DM or serum TgAb, TSH, T4, and T3 concentrations. The present study suggests that oral tolerization with hTg does not affect spontaneous or iodine-induced lymphocytic thyroiditis or serum thyroglobulin antibodies in the BB/Wor rat.