The effects of aging on human or animal thyroid function are still not well defined. We evaluated some aspects of thyroid function during aging using an animal model (young and old Dutch-Miranda rats). In old rats of both genders, serum thyroxine (T4) decreased but serum thyrotrophin (TSH) remained unaltered, suggesting a disturbance in the pituitary-thyroid feedback mechanism during aging. Serum tri-iodothyronine (T3) only decreased in old males, possibly because female rats are almost twice as efficient in hepatic T4 to T3 deiodination. Thyroidal T4-5'-deiodinase activity did not change much during aging, although it decreased slightly in males. Thyroidal iodothyronine-deiodinase type I mRNA expression but not total thyroidal enzymatic activity were higher in female than in male rats. Thus, ovarian/testicular hormones may modulate the expression and/or the activity of hepatic and thyroidal type I iodothyronine-deiodinase. Thyroperoxidase (TPO) and thyroglobulin (Tg) expression were higher in young male rats than in females. In males, TPO and Tg gene expression decreased with aging, suggesting that androgens might increase their expression. Our results showed that aging induces real changes in rat thyroid gland function and regulation, affecting at least pituitary, thyroid and liver functions. Furthermore, some of these changes were gender related, indicating that gonadal hormones may modulate thyroid gland function and regulation.