Thyrotropin releasing hormone (TRH) administered both intraventricularly and parenterally suppressed stress induced eating (using the mild tail pinch model) in a dose related manner. This suppression was partially reversed by intraventricular administration of the long acting synthetic enkephalin analog, D-Ala-Met-Enkephalin (p < 0.01). Preliminary data suggests that the naturally occurring metabolic breakdown product of TRH, histidyl-proline-diketopiperazine, may be the active substance with TRH acting as a pro-hormone. The TRH effect was present in hypophysectomized animals showing that the TRH-induced decrease in food ingestion was not secondary to an increase in thyrotropin or thyroid hormones. TRH did not alter blood glucose levels. Our data is compatible with a possible physiological role for TRH, as a peptidergic mediator of satiety acting as a direct antagonist of the lateral hypothalamic of satiety acting as a direct antagonist of the lateral hypothalamic enkephalin-mediated feeding center.