The BB/Wor rat develops spontaneous insulin dependent diabetes mellitus (DM) and lymphocytic thyroiditis (LT). We have recently demonstrated that immunization of BB/Wor rats with allogeneic thyroglobulin (Tg) induces LT at an early age. The incidence of spontaneous and Tg induced LT is extremely variable among different BB/Wor sublines. It has been shown that high iodine diet significantly increases the incidence of spontaneous lymphocytic thyroiditis (LT) and low iodine diet significantly decreases the incidence of LT in genetically predisposed BB/Wor rats. Recent studies on thyroglobulin (Tg) induced LT in chicken and mouse have shown that iodine rich Tg is far more antigenic than Tg with a low iodine content, suggesting that a high iodine diet increases the immunogenicity of Tg molecule. In order to determine whether the extent of Tg iodination would affect its immunogenicity in the BB/Wor rats, the current study was carried out. Normal iodine Tg (NTg) or low iodine Tg (LTg) was obtained from thyroids of rats that were placed on regular diet or regular diet plus 0.5% methimazole, respectively. 120 rats from the NB (highly susceptible) and BB (low susceptible) sublines were randomized in three groups. Immunization was carried out with a 1:1 emulsion of complete Freund's adjuvant (CFA) and LTg, NTg (0.6 mg/rat) or saline at 30 and 37 days of age. Since spontaneous LT rarely occurs before age 75 days, rats were sacrificed at age 65 days to specifically study Tg induced LT. Immunization with NTg induced LT in 31% of the NB rats, but not in the BB subline. LTg did not induce LT in either subline. Tg antibody (Ab) OD's were higher in the NB rats in all immunization protocols and also significantly higher in each strain of rats immunized with NTg compared with LTg. Serum T4ab were present in both sublines immunized with NTg. Serum TSH concentrations and BEI were normal and similar in both sublines confirming the euthyroid status of these rats. These findings demonstrate that, in this animal model, I may play an important role in the induction of LT. Importance of a genetically susceptible background in order to trigger autoimmunity is emphasized.