Corticotropin-releasing factor-containing cells have been recently found in the endocrine pancreas of several vertebrate species by immunocytochemistry. In order to clarify the possible physiological significance of these findings, we have studied the effect of the administration of CRF on endocrine pancreatic function. Five minutes, after injection of ovine CRF 1-41 into the jugular vein, a dose-related increase in insulin levels in the hepatic-portal vein of anesthetized rats was found. This dose-dependent insulin increase was delayed to fifteen minutes after CRF injection into rats exposed to greater surgical stress and was partially blunted in adrenalectomized animals. Glucose and glucagon levels were not altered after CRF administration under these conditions. These results suggest that CRF may play a modulatory role in insulin secretion; however, whether CRF acts directly on the beta-cell or through some CRF-stimulated mediator remains to be established.