Brain hormones exquisitely regulate the secretion of hormones secreted by the pituitary gland that affect onset of puberty and reproductive function in pigs. Luteinizing hormone releasing hormone (LHRH) is a hypothalamic 10-amino acid peptide produced by a small placode of LHRH neurons (~1,500) that is crucial for gonadotropin (LH and follicle stimulating hormone, FSH) release by the pituitary gland. Neurosurgical interventions obliterate LHRH release thus interfering with episodic LH and FSH secretion required for continued reproductive function in male and female pigs. The hypothalamus at the base of the brain regulates episodic LH and FSH secretion from the pituitary in part by its endogenous release of LHRH and by feedback effects of gonadal protein (i.e., inhibin) and steroid (i.e., estrogen, progesterone, androgen) hormones. The objectives were to determine hypothalamic regulation of episodic LH secretion in female pigs and the biphasic feedback actions of estradiol-17 beta (E₂-17β). Ovariectomy of gilts eliminates negative feedback effects of estrogen on the brain and thus allows an elevated level of episodic LH secretion compared with intact control animals. Neurosurgical disconnection of the neurohypophyseal link between the hypothalamus and pituitary (hypophyseal stalk transection, HST) blocks hypothalamic LHRH secretion to the pituitary gland, eliminating episodic LH secretion that renders the animal acyclic. In this study, the minimum effective dosage of E₂-17β that would induce estrus in ovariectomized gilts was determined to be 20 µg/kg body weight. Then, ovariectomized gilts were assigned randomly to HST, cranial sham operation control (SOC), and unoperated control (UOC). In HST gilts, episodic LH release was abolished and average LH blood concentration decreased compared with controls. E₂-17β or sesame oil vehicle did not affect blood LH concentration in HST gilts, and LH remained constant throughout 120 hours (0.7 ng/ml). In contrast in the SOC and UOC gilts, E₂-17β induced a 60% decrease in LH concentration within 12 hours, and LH remained low until 48 hours, then increased to peak values by 72 hours, and was followed by a decline to 120 hours. These results indicate that both episodic LH secretion and the biphasic feedback action of E₂-17β on LH secretion depend on hypothalamic regulatory mechanisms in the gilt. The isolated pituitary in HST gilts is capable of autonomous secretion of LH, E₂-17β will elicit direct negative feedback action on the isolated pituitary gland if the gonadotropin-producing cells in that gland are supported by exogenous LHRH, but E₂-17β at high concentrations will not induce positive feedback in isolated pituitaries.