Prolonged administration of 25 mg iodide per day to euthyroid subjects caused an increased release of HTSH in response to the i.v. administration of TRH. This effect was significant (p less than 0.01) intraindividually in eight out of nine subjects. The maximum serum HTSH level was observed twenty minutes after the administration of TRH. It reached 8.0 +/- 1.7 muU/ml during the control period and increased to 11.6 +/- 1.6 muU/ml after two weeks of 25 mg iodide per day. Basal serum concentrations of HTSH remained unchanged (p less than 0.05) and were 1.2 +/- 0.3 muU/ml before, and 1.7 +/- 0.3 muU/ml after iodide ingestion. Basal serum T4 concentrations and T4 release were diminished after prolonged administration of iodide in the nine subjects on the basis of an intraindividual comparison. Serum triiodothyronine showed a similar behavior as far as basal conditions were concerned, but no difference was observed for the peak levels of T3, which were obtained 2 to 3 h after injection of 400 mug TRH. The obtained data show that the prolonged ingestion of iodide induces a relatively hypothyroid state with an increased release of HTSH in response to the injection of TRH. This effect is paralleled by a decreased secretion of thyroxine and, to some extent, of triiodthyronine. The Wolff-Chaikoff effect, which is induced by the administration of excess iodide, appears to be the cause of the observed increase in TSH secretion upon TRH administration in iodide-treated subjects.