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Investigation of thyroid glands from 500 male and 500 female Sprague-Dawley rats, at time points of 8, 17, 30, 56, and 108 weeks of toxicity studies conducted at the Huntingdon Research Centre between 1981 and 1984, revealed age-related structural and functional changes that have previously not been well documented. The number of ultimobranchial cysts decreased with age, while area(s) of C-cell hyperplasia appeared with age. Beginning at 56 weeks, some of the thyroid follicles were hyperdistended with colloid, had irregular lumens, and were lined by flattened epithelium. These follicles had clumped, granular, and stratified colloid. Follicular tumors were found in 8% of the males and 6% of the females at 108 weeks. There was an increase in absolute thyroid weights (males from 21.8 +/- 4.0 g to 46.5 +/- 19.05 g, females from 17.2 +/- 4.53 g to 41.7 +/- 26.92 g) and body weights (males from 382.0 +/- 70.6 g to 806.0 +/- 120.7 g, females from 220.0 +/- 21.0 g to 495.0 +/- 127.3 g) with age in both sexes, but the relative thyroid weights were not significantly affected. Negative allometry was observed. With an increase in the age of the rats, there was a decrease in the height of the follicular epithelium and an increase in the internal follicular diameter and the total number of follicles. No prediction for sex could be detected. Serum T3 and T4 concentrations were constant until 56 weeks of age, but at 108 weeks, the values were markedly reduced (in males, serum T3 concentration decreased from 91.60 +/- 13.970 ng/100 ml to 32.90 +/- 10.878 ng/100 ml, and in females, from 90.80 +/- 11.338 ng/100 ml to 48.10 +/- 8.875 ng/100 ml; in males, serum T4 concentration decreased from 5.94 +/- 0.679 microgram/100 ml to 3.04 +/- 0.604 microgram/100 ml, and in females, from 4.59 +/- 0.717 microgram/100 ml to 2.77 +/- 0.786 microgram/100 ml). The data suggest that the thyroid function of Sprague-Dawley rats reduces as the rats age.