The previously described peptidic material that reacts with antibodies to gastrin and is found in the central nervous system of various vertebrates is present in only the 100,000 X g pellet of postmortem human cerebral cortical irey matter. This immunoreactive material, extractable in boiing water, is biologically active on rat pancreatic preparations. On the basis of size, charge, immunological specificity, and patterns of biological activity, most of this material is closely related to the COOH-terminal octapeptide of cholecystokinin in its complete, sulfated biologically active form.A number of hypothalamic peptides, such as thyrotropin-releasing hormone (1), luteinizing hormone-releasing hormone (2), somatostatin (3), and substance P (4), have been shown to be present in the cerebral cortex. It has been hypothesized that the extrahypothalamic localization of these peptides may result from the existence of peptidergic hypothalamocortical pathways (5). Some of these hypothalamic peptides, such as substance P and somatostatin (6, 7), have also been detected in the digestive tract.These observations, and Pearse's theory (8) of an embryological relationship between the nervous system and gut endocrine cells, have led Vanderhaeghen et al. (9) to search for and find immunologically active gastrin-like peptidic material (BGP) in the central nervous system (CNS) of various vertebrates. BGP was found at concentrations as high as 30 pmol of gastrin equivalent per g of wet weight. This raises the possibility of synthesis of BGP within the CNS. Because concentrations of BGP were maximal in the cerebral cortex and striatum, a hypothalamic origin of BGP is unlikely. Elution patterns of BGP on Sephadex G-50 show a lower molecular weight than gastrin-(2-17)-hexadecapeptide, and the analysis of radioimmunoassay dose-response curves shows immunological differences between gastrin-(2-17)-hexadecapeptide and BGP.The search for digestive peptides in the CNS is currently expanding rapidly. Vasoactive intestinal polypeptide (VIP) has been detected in the brain (10-12), pancreatic polypeptide (PP) has been found in earthworm neurons and processes (13), and bombesin may be present in the brain (14). Conversely, neurotensin (15) and opioids (16) have been discovered in the digestive system. From the above considerations emerges the concept of the existence of a large number of peptides common to the nervous and digestive systems.The existence of BGP has been confirmed by several authors. The differences reported between gastrin and BGP (9) have been explained by the close immunuological relationship of BGP