To determine whether endogenous prostaglandins (PGs) are involved in the secretion of thyrotropic hormone (thyrotropin, TSH), plasma TSH levels were monitored in female rats receiving indomethacin (Ind) or aspirin (Asp) to inhibit PG synthesis. TSH secretion was induced by either exogenous thyrotropin-releasing hormone (thyroliberin, TRH) or by thyroidectomy. On the basis of preliminary experiments, Ind inhibited thyroid secretion directly. Subsequently, thyroidectomized rats receiving thyroxine (T4) replacement (2-4 .mu.g/100 g body wt/day) were used to avoid this complicating factor. These replacement regimens were judged to be adequate on the basis of the measurement of plasma triiodothyronine and T4 levels, and the lack of a compensatory rise in plasma TSH levels. Under these conditions, Ind significantly inhibited, but did not abolish, the TSH response to exogenous TRH (250 ng/100 g body wt i.v.). Thyroidectomy-induced TSH secretion was abolished by Ind and could be reversed upon cessation of Ind treatment. Aspirin also inhibited significantly the compensatory TSH rise following thyroidectomy. Endogenous pituitary PGs may mediate the stimulation of TSH secretion by TRH or by reduced feedback of thyroid hormones.