The changes in serum triiodothyronine (T3), thyroxine (T4), and thyrotropin (TSH) were measured during iodine repletion in a woman who was severely iodine-deficient because of a congenital iodide-trapping defect. Serum T3 became detectable 12 h after iodine was begun and reached 68 ng/dl, a level within the normal range, by 36 h. It rose progressively during the first 9 days reaching a supra-normal level (200 ng/dl) and then fell slowly to 130 ng/dl. Serum T4 was not detected (less than 1 mug/dl) until the 9th day and then rose to 6.8 mug/dl. Serum TSH fell rapidly during the first 9 days (disappearance rate was 0.17/day); there was a significant negative correlation with serum T3 (P less than 0.01). From the 10th through the 32nd day serum TSH fell more slowly (disappearance rate was 0.05/day) and correlation was with serum T4 (P less than 0.001), not T3. It appears that either T3 or T4 may regulate TSH secretion by direct effects on the thyrotroph, although their intracellular mode of action has not been defined.