The effects of overfeeding and triiodothyronine (T3) administration on basal serum thyrotropin (TRH) concentrations and the TSH response to thyrotropin-releasing hormone (TRH) was studied in normal subjects. Eight normal volunteers were fed their usual diet plus 2,000 kcal carbohydrate daily for 7 days. Their mean serum T3 concentrations increased from 102 +/- 6 (SEM) ng/dl to 126 +/- 10 ng/dl; there were no changes in serum thyroxine (T4) and basal serum TSh concentrations or the TSh response to TRH. Five of these subjects were fed their usual diet plus 10 micrograms T3 for 3 days and 20 micrograms T3 for 4 days divided doses. Their mean serum T3 concentrations increased from 104 +/- 6 ng/dl to 140 +/- 8 ng/dl. Mean serum T4 and basal serum TSH concentrations declined and serum TSH responses to TRH were significantly reduced. In both instances serum T3 concentrations remained within the normal range. These results indicate that increases in serum T3 concentrations of similar magnitude induced by augmented extrathyroidal T3 production and T3 administration have different effects on thyrotroph function.