A rich network of NPY-like immunoreactive fibers was found in the paraventricular nucleus and the ventromedial region of the hypothalamus juxtapositioned to the third ventricle, including the median eminence. Brain regions, areas or nuclei found densely innervated by NPY-like immunoreactive fibers included the olfactory bulb region, septal area, organum vasculosum of the lamina terminalis, preoptic periventricular nucleus, hypothalamic periventricular nucleus, medial suprachiasmatic nucleus, subseptal (subfornical) organ, ventromedial hypothalamic nucleus, infundibular nucleus and nucleus tractus solitarius. NPY-like containing perikarya were localized within the hippocampus, bed nucleus of the stria terminalis and surrounding the nucleus rotundus and nucleus of the basal optic root. Since the immunocytochemical study showed that NPY was localized in brain structures known to alter food intake and the compound is a member of the pancreatic polypeptide family, a second study was designed to determine if the neuropeptide altered plasma concentrations of insulin, glucagon and glucose following intracerebroventricular administration. It was found that NPY significantly increased plasma concentration of insulin. It is proposed that two reasons why NPY is such a potent orexigenic agent is that the paraventricular nucleus and structures surrounding the third ventricle throughout the ventromedial hypothalamic region show high levels of NPY-like immunoreactivity. Secondly, NPY effects an increase in plasma insulin in the periphery.