The influence of the opioid peptide dermorphin on 2DG-stimulated pancreatic secretion of the rat was studied. Experiments were performed in conscious rats with pancreatic fistulae (8 animals), or with pancreatic and gastric fistulae (8 rats) to allow diversion of gastric juice. In animals with gastric fistulae the peak of pancreatic protein output in response to 2DG was about 50% lower than in animals with intact stomachs. Dermorphin almost completely inhibited the stimulant effect of 2DG, independently by different experimental conditions. It is concluded that the increase of pancreatic secretion produced by 2DG is, at least in part, independent from the entrance of gastric acid into the duodenum. As a consequence, the inhibiting effect of dermorphin on 2DG-stimulated pancreatic secretion may be attributed to a decrease of vagal stimulation of the pancreas, at central and/or peripheral sites.