Mucus and bicarbonate secreted from the epithelium are thought to be important for the protection of the duodenal mucosa against acid and pepsin, but so far little is known about the regulation of human duodenal mucosal bicarbonate secretion. After isolating a segment of the proximal human duodenum from gastric and pancreaticobiliary secretion we quantified the secretion of bicarbonate from the human duodenal mucosa. The method was evaluated by measurements of basal and prostaglandin E1 analogue-stimulated bicarbonate secretion. The duodenal mucosal bicarbonate secretion was inhibited 70% after intravenous infusion of morphine in a dose of 73.6 micrograms/kg/h and increased after intravenous administration of naloxone. Thus, the inhibition is most likely mediated by mu-receptors, and the results suggest a role of endogenous opioids in the regulation of the secretion of bicarbonate from the human duodenal mucosa.