During fetal development the neuroendocrine system plays a pivotal role in the regulation of normal intrauterine development, growth and differentiation and the onset of birth. Studies on the ontogenic development of neuroendocrine function in sheep fetuses are discussed with particular reference to the differential regulation of the pituitary-gonadal and pituitary-adrenal axis. Fetal pituitary-gonadal activity increases to a maximum at mid-gestation and is suppressed just before birth. Using immunocytochemistry, we have examined the ontogeny of gonadotroph development in the pituitary of female sheep fetuses. At day 70 of gestation (term = 145 days) only immunopositive luteinizing hormone beta (LH beta) cells were present. The number and intensity of staining of these LH beta cells increased by day 100 and declined again by day 130. Immunopositive alpha-subunit and follicle-stimulating hormone beta (FSH beta) cells appeared by day 100 of gestation and had further increased in number and staining intensity by day 130. Treatment of fetuses with the gonadotrophin-releasing hormone (GnRH) agonist, buserelin, from day 70 of gestation results in desensitization of the fetal pituitary gonadotrophs, suppression of pituitary gonadotrophin mRNA and a reduction in the number of immunopositive gonadotrophin-containing cells. Thus, in sheep fetuses the development of cells containing LH and FSH depends critically on an appropriate GnRH signal from the fetal hypothalamus. In contrast, hypothalamo-pituitary-adrenal activity increases during gestation to reach a maximum before birth. This is characterized by a progressive increase in fetal plasma adrenocorticotrophic hormone (ACTH) and cortisol concentrations, and a high frequency of ACTH and cortisol pulses in the final hours before parturition. Steady state concentrations of pro-opiomelanocortin (POMC) mRNA increase throughout fetal development but decline dramatically in the final days before birth, when ACTH concentrations are at a maximum. This decline in POMC expression is probably the result of the negative feedback effects of high cortisol concentrations. The neuroendocrine mechanisms that mediate the pulsatile secretion of ACTH at this crucial time are complex and as yet incompletely defined. However, the opioid antagonist, naloxone, suppresses the secretion of ACTH during the final days before birth, thus providing evidence for the tonic regulation of ACTH secretion by stimulatory endogenous opioids. Prostaglandins that are secreted from the placenta during late gestation stimulate fetal ACTH, but not gonadotrophin secretion, whereas placental steroids are thought to inhibit fetal gonadotrophin secretion.(ABSTRACT TRUNCATED AT 400 WORDS)