As the first known of the mammalian brain's neuropeptide systems, the magnocellular hypothalamo-neurohypophysial system has become a model. A great deal is known about the stimulus conditions that activate or inactivate the elements of this system, as well as about many of the actions of its peptidergic outputs upon peripheral tissues. The well-characterized actions of two of its products, oxytocin and vasopressin, on mammary, uterine, kidney and vascular tissues have facilitated the integration of newly discovered, often initially puzzling, information into the existing body of knowledge of this important regulatory system. At the same time, new conceptions of the ways in which neuropeptidergic neurons, or groups of neurons, participate in information flow have emerged from studies of the hypothalamo-neurohypophysial system. Early views of the SON and PVN nuclei, the neurons of which make up approximately one-half of this system, did not even associate these interesting, darkly staining anterior hypothalamic cells with hormone secretion from the posterior pituitary. Secretion from this part of the pituitary, it was thought, was neurally evoked from the pituicytes that made the oxytocic and antidiuretic "principles" and then released them upon command. When these views were dispelled by the demonstration that the hormones released from the posterior pituitary were synthesized in the interesting cells of the hypothalamus, the era of mammalian central neural peptidergic systems was born. Progress in developing an ever more complete structural and functional picture of this system has been closely tied to advancements in technology, specifically in the areas of radioimmunoassay, immunocytochemistry, anatomical tracing methods at the light and electron microscopic levels, and sophisticated preparations for electrophysiological investigation. Through the judicious use of these techniques, much has been learned that has led to revision of the earlier held views of this system. In a larger context, much has been learned that is likely to be of general application in understanding the fundamental processes and principles by which the mammalian nervous system works.(ABSTRACT TRUNCATED AT 400 WORDS)