Two experiments were conducted to test the hypothesis that thyroid hormones exert central negative feedback effects on the secretion of TRH from the hypothalamus in the ewe. In the first experiment, we examined the effects of thyroidectomy on the secretion of TRH and TSH. Thyroidectomy was followed by an unambiguous increase in TRH in pituitary portal plasma and TSH in the peripheral circulation. In the second experiment, we tested the effects of T4 replacement to thyroidectomized ewes. T4 replacement reversed the effects of thyroidectomy on TRH and TSH release. Of interest, TRH secretion in thyroidectomized ewes was continuously elevated during the collection, raising the possibility that TRH is secreted continuously, rather than exclusively in a strictly pulsatile manner indicative of phasic discharges synchronized among TRH neurosecretory elements. Collectively, these results suggest that thyroid hormones can act centrally to inhibit TRH (and thus TSH) release in the ewe, and they support the concept that at least part of the negative feedback action of thyroid hormones is exerted at the hypothalamic level.