CRF has been detected in the endocrine pancreas by immunocytochemistry with an antiserum that recognizes mainly the C-terminal portion of CRF-41. CRF-containing cells have been shown to be present in the pancreas of representative species of fishes, amphibians, reptiles, birds, and mammals including man. Light and electron microscopic observations indicate that the CRF-containing cells in the endocrine pancreas are similar to glucagon (A) cells both in their morphology and distribution. Individual CRF-containing cells are also found scattered in the exocrine pancreas in all species studied. In addition, CRF-containing cells have been identified in the human, monkey, cat, and rat stomach and small intestine. Recent reports also indicate that CRF-like immunoreactivity is present in the circulating blood, the adrenal medulla, and the placenta. Finally, several peripheral (pancreas, stomach, colon, lung and thyroid) tumors which produced corticotropin-releasing substances have been described by others. Although the peripheral actions of CRF are not yet known, these observations indicate that it is widely distributed in peripheral tissues and it may also represent a new tumor marker.