In order to identify the changes in thyroid regulation and function that are responsible for the age-related decline in T4 secretion, we measured the secretory response of the rat pituitary and thyroid glands to thyrotropin-releasing hormone (TRH), plasma T1/2 for 125I-rat thyrotropin (TSH), the molecular weight of pituitary TSH, T4 uptake and conversion to T3 by the liver, amount of T4 and T3 in serum and in thyroglobulin, and the thyroid peroxidase concentration. The molecular weight of TSH and the biexponential plasma clearance of TSH were not affected by aging. TSH response to TRH administered intravenously did not differ between old and young rats. T3 response to TRH was greater and T4 response lower in old compared with young rats despite levels of T4 and T3 in thyroglobulin which were not affected by aging. Aging effects on hepatic conversion of T4 to T3 varied between rat strains. T4 uptake by liver in vivo by old rats was the same as that reported for young animals. The data are consistent with a marked decrease in the ratio of T4 to T3 secreted by the aging rat thyroid in both the basal and stimulated state possibly due to increased intrathyroidal conversion of T4 to T3.