We have recently reported that iodine administration (0.05% iodine in drinking water) to weanling, diabetes mellitus- and lymphocytic thyroiditis (LT)-prone Biobreeding Worcester (BB/W) rats strikingly increases the incidence of LT without occurrence of iodine-induced hypothyroidism, which frequently results when excess iodine is administered to euthyroid patients with Hashimoto's thyroiditis. Since hypothyroidism did not occur in the iodine-treated BB/W rats, hemithyroidectomy was carried out in 30-day-old BB/W rats to increase thyroid mass and functional reserve. Iodine administration for 60 days markedly increased antithyroglobulin antibodies (0.40 +/- 0.08 vs. 0.15 +/- 0.06 OD; P less than 0.02), the incidence of LT (68% vs. 13%; P less than 0.001), and thyroid weight of the residual lobe (10.5 +/- 0.7 vs. 6.3 +/- 0.3 mg/100 g BW; P less than 0.001) and induced hypothyroidism (T4, 2.5 +/- 0.2 vs. 3.0 micrograms/dL; P less than 0.05; T3, 25.1 +/- 1.9 vs. 37.5 ng/dL; P less than 0.001; TSH, 252 +/- 49 vs. 61 +/- 14 microU/mL; P less than 0.02). Hypothyroidism in the iodine-treated rats occurred primarily in those with LT. Similar studies were carried out in the non-diabetes mellitus-, non-LT-prone, genetically equivalent BB/W rats (W-line), the parent strain Wistar-Furth rats, and Sprague-Dawley rats. Iodine administration did not induce LT or antithyroglobulin antibodies in these three strains and did not affect thyroid function in Wistar-Furth and Sprague-Dawley rats. However, in the W-line rats, iodine excess did induce thyroid enlargement in the residual lobe (8.4 +/- 0.2 vs. 6.4 +/- 0.2 mg/100 g BW; P less than 0.001), a decrease in serum T3 (71.5 +/- 2.9 vs. 86.0 +/- 2.5 ng/dL; P less than 0.001), and an increase in serum TSH (344 +/- 65 vs. 69 +/- 6.0 microU/mL; P less than 0.001). It is evident, therefore, that hemithyroidectomy in BB/W rats sufficiently reduces functioning thyroid tissue, resulting in iodine-induced LT and hypothyroidism, similar to iodine-induced hypothyroidism in euthyroid patients with Hashimoto's thyroiditis. It is unclear, however, why iodine administration also induced hypothyroidism in hemithyroidectomized, genetically similar, W-line rats in the absence of LT. This observation suggests that iodine-induced hypothyroidism in rats may be genetically determined.