Age-related thyroid changes, such as those in weight, histology, morphometry, and hormonal concentrations were evaluated in 460 male and 460 female F344 rats from 9 to 109 weeks of age. The absolute weight of the thyroid increased with age in both sexes, but the relative weight was unaffected by age. Ectopic thymus and ultimobranchial cyst were observed in rats of both sexes from 9 to 109 weeks of age. The incidence of both congenital anomalies decreased with age. The incidence of follicular cyst, which was first observed in rats at 20 weeks of age, increased at 109 weeks. Hyperdistention of the follicle with infiltration of macrophages in the lumen and deposition of brown pigments in the cytoplasm of epithelial cells were observed in a few rats at 59 weeks of age. These follicular lesions were found in 29% of the males and 7% of the females at 109 weeks. The first thyroid tumor was seen at 59 weeks of age. In 109-week-old rats, 5% of males had follicular tumors, and 18% of males and 10% of females had C-cell tumors. At 82 weeks of age, the follicular area and the area of the follicular lumen increased, and the height of follicular epithelial cells decreased. Serum T3, T4 and TSH concentrations decreased with age and were significantly reduced at 82 weeks. These results suggest that in F344 male rats the thyroid structural and functional changes occurred with age, and thyroid function decreased after 82 weeks of age.