Since the chemical identification of gonadotropin-releasing hormone (GnRH) in 1971, significant progress has been made in understanding the mechanisms by which GnRH action is mediated in the anterior pituitary. In contrast, relatively little information is available which identifies the intracerebral sites and mechanisms of action of GnRH in the brain. Early immunohistochemical studies of GnRH distribution in the central nervous system, together with behavioral and electrophysiological experiments, suggested that GnRH functioned as a neurotransmitter and was, possibly, involved in the expression of reproductive behaviors. The subsequent identification and characterization of GnRH receptors in the brain further strengthened the view that GnRH caused specific effects in select regions of the brain known to be involved in the neuroendocrine regulation of the anterior pituitary and in the generation of reproductive behaviors. After the mouse pituitary GnRH receptor was cloned it became possible to identify brain neurons which contained the GnRH receptor mRNA. Comparison of the locations of the GnRH peptide, the GnRH receptor protein, and the neurons which contain the GnRH receptor mRNA suggests that the GnRH neuronal system itself can potentially provide a direct link between the neuroendocrine regulation of anterior pituitary function and the intracerebral regulation of reproductive behaviors; furthermore, it is possible that the GnRH neuronal system takes an active part in intracerebral feedback loop systems between the mediobasal hypothalamus and the septum-diagonal band which regulate GnRH release from the median eminence. (C) 1994 Academic Press, Inc.