Using antiserums generated against the neuropeptides corticotropin-releasing factor (CRF), beta-endorphin, and adrenocorticotropin, we have immunocytochemically mapped the organization of these hormones throughout the brain. The distribution of CRF perikarya is widespread throughout the forebrain, brain stem, and spinal cord. The central opiomelanocortin system is represented by two separate pools of neuronal perikarya: the hypothalamic arcuate pool, and the medullary (nucleus tractus solitarius) pool. From these groups fibers distribute widely throughout forebrain and brain stem. A conspicuous codistribution pattern exists between the CRF perikarya and opiomelanocortin fibers. Analysis of these systems within the brain stem and spinal cord reveals innervation and distribution patterns within regions containing catecholamine systems, areas associated with regulation of sympathetic and parasympathetic outflow, cardiovascular and respiratory homeostatic centers, and regions associated with stress, autonomic homeostasis, and pain modulation. By virtue of these extensive brain-stem distributions, it is suggested that an anatomical substrate exists for participation of these peptide systems in the integration of certain autonomic, visceral, and homeostatic mechanisms.