AVP and CRH produced in the parvocellular neurons of the paraventricular nucleus (PVN) have both been implicated in the regulation of anterior pituitary ACTH synthesis and secretion. In sheep, fetal ACTH secretion increases around 120 days gestational age (dGA). Little is known about adrenal regulation of AVP and CRH immediately prior to this critical period. We investigated the effects of adrenalectomy and subsequent cortisol (F) administration on PVN AVP and CRH mRNA in the fetal sheep PVN at 109-125 dGA. At 109-113 dGA, fetal sheep adrenals were removed (ADX)(n = 8); or sham surgery performed (CONT)(n = 4). From day 6 post ADX, maternal plasma cortisol and fetal plasma ACTH and cortisol levels were determined daily by radioimmunoassays. From day 7 post ADX, cortisol (4 micrograms/min) was continuously infused intravenously to four ADX fetuses (ADX + F). Fetal hypothalami were collected at 123-125 dGA, and studied by in-situ hybridization and quantitative autoradiography for AVP and CRH mRNA. Plasma cortisol levels remained low in CONT and ADX fetuses (< 4.9 ng/ml), while during cortisol infusion to ADX + F fetuses, plasma F increased to 16.4 +/- 2.2 and 22.3 +/- 3.2 ng/ml (mean +/- S.E.M.) on day 10 and 13, respectively. Plasma ACTH levels increased significantly in ADX compared with CONT fetuses. This ACTH increase was completely suppressed in ADX + F fetuses. AVP mRNA abundance in the whole PVN was the same in all three groups, however, a separate analysis of AVP mRNA abundance in parvocellular and magnocellular regions of the PVN revealed that AVP mRNA in the parvocellular PVN showed a significant increase in ADX and suppression in ADX + F fetuses when compared to CONT. AVP mRNA in the magnocellular PVN remained unchanged. PVN CRH mRNA expression was augmented in ADX and suppressed in ADX + F when compared to CONT fetuses. We conclude that in fetal sheep at 109-125 dGA: AVP and CRH mRNA abundance in the parvocellular region of the PVN are increased by adrenalectomy and that cortisol inhibits this increase.