Arachidonic acid metabolites have been shown to modulate the secretion of various hormones, including luteinizing hormone, growth hormone and adrenocorticotropin. In this paper we describe the effect of a series of eicosanoids on hypothalamic secretion of corticotropin-releasing hormone (CRH) in vitro. Explanted rat hypothalami in culture were exposed to prostaglandins (PG) F2 alpha or E2, thromboxane (TX) B2, the TXA2 receptor agonist U-49,619 and leukotrienes (LT) B4, C4 and D4 at concentrations ranging from 10(-15) to 10(-5) M. PGE2, LTD4 and TXB2 did not alter hypothalamic CRH secretion. On the other hand, the remaining eicosanoids tested induced a significant increase of hypothalamic CRH secretion (p less than 0.05). The concentration of 10(-11) M dexamethasone inhibited the effect of stimulatory eicosanoids on CRH secretion. The CRH response to U-49,619 was completely prevented by the TXA2 receptor antagonist SQ-29,548. The latter also inhibited serotonin (5-HT)-, acetylcholine (ACh)- and PGF2 alpha-induced CRH release. Indomethacin was capable of blocking the secretion of CRH induced by 5-HT and ACh. In addition, PGE2 inhibited the increase of CRH secretion induced by PGF2 alpha, 5-HT and ACh. These findings suggest that eicosanoids may be involved in the regulation of hypothalamic CRH secretion, either as autocrine/paracrine or as endocrine factors.