Abstract. In 17 euthyroid normal volunteers and 17 hypothyroid patients, serum concentrations of TSH, T3 and T4 were measured after multiple stimulations with TRH. All subjects received 6 TRH-injections (200 μg iv) at intervals of 2 h. Three euthyroid normal volunteers were stimulated 12 times with TRH in the same way. The TSH response (ΔTSH) was significantly decreased (P<0.01) after the 4th injection, and after the 5th of 6th stimulation, it was significantly raised (P<0.02) compared with the 4th. In the case of the 12-fold stimulations, the ΔTSH also rose after the 9th or 10th injection compared with the response after the 8th of 9th. In 5 of the 17 normals, the increase in ΔTSH observed after the 5th or 6th TRH-injection was greater than the ΔTSH after the first stimlation. Serum T3 and T4 levels rose already after the first TRH-stimulation (P<0.01) and remained at these increased levels thereafter. The hypothyroid patients also showed initial decrease of ΔTSH (P<0.01). The increase of the TSH-response to TRH, however, was observed after the 4th TRH-injection (P<0.05) rather than after the 5th or 6th, followed by another decrease of ΔTSH after the 5th stimulation (P = 0.02). In 11 of the 17 hypothyroid patients, there was a second increase of ΔTSH after the 6th TRH-stimulation. This second increase was greater than the first in 10 of the 11 subjects. Serum T3 and T4 levels in the hypothyroid subjects remained unchanged during the entire examination period. From these results, it can be concluded that the cause for the TSH response pattern in TRH-stimulations repeated at brief intervals cannot be due to the feed-back of thyroid hormones, but rather to the activity of TSH-producing pituitary cells.