The light microscopic immunocytochemical localization of corticotropin-releasing factor (CRF) is described in the endocrine pancreas of several species representing the major classes of vertebrates: fishes (channel catfish, Ictalurus punctatus), amphibians (African clawed toad, Xenopu8 laevis), reptiles (chameleon, Anolis carolinensis), birds (chicken, Gallus domesticus), and several mammals (rat, mouse, cat, rhesus monkey, and man). The CRF-containing cells are scattered over the entire islet tissue in primates and cat, whereas in rat and mouse they are located at the periphery of the islets. In the chicken and catfish, the CRF-containing cells are found in a central location within islets and form larger clusters or cords. Single cells with CRF-like immunoreactivity are interspersed between acinar cells of the exocrine pancreas in all species studied. The CRF cells show a substantial topographical overlap with glucagon cells, but their precise identity and function remain to be determined.Corticotropin-releasing factor (CRF), a 41-amino acid peptide, has been isolated and characterized from extracts of ovine hypothalamus as a potent stimulator of the secretion of corticotropin (ACTH) and 3-endorphin (1-3). Immunocytochemical studies have established that most of the CRF in the hypothalamus is located both in neurons of the paraventricular nucleus and in terminals around portal capillaries of the median eminence (4-7). CRF-like immunoreactivity has been identified in hypophysial portal blood (8). The neural pathways through which CRF reaches the median eminence also have been described (9). Like other neuropeptides, CRF is widely distributed in extrahypothalamic areas of the brain, determined by both radioimmunoassay (10) and immunocytochemistry (11)(12)(13). In addition to stimulating the release of ACTH and /8-endorphin, CRF has a broad range of pharmacological effects, which include changes in behavior, heart rate, blood pressure, and in blood concentrations of epinephrine, norepinephrine, glucagon, and glucose (14-18). Thus, CRF appears to be an important regulatory peptide mediating stress-related physiological responses and predictably possessing other, hitherto unsuspected, hormone-or neurotransmitter-like activities. On the basis of current hypotheses concerning the common evolutionary origin of hormones and neurotransmitters (19)(20)(21) (Altamont, NY). One African clawed toad (Xenopus laevis) and pancreatic tissue from two channel catfish (Ictalurus punctatus) were gifts from L. J. Haverkamp (Neurobiology Program, University of North Carolina) and J. E. Brinn (Department of Anatomy, East Carolina University), respectively. Three lizards (Anolis carolinensis) were purchased from Carolina Biological Supply (Burlington, NC). Pancreatic tissue from two adult cats and two adult rhesus monkeys (Macaca mulatta) also was studied. Human pancreas (courtesy of E. K. MacRae and F. D. Dalldorf) was from a 1-year-old infant who died in an accident.Preparation of Tissues. Rat, mouse, cat, monkey, chicken, ...