Intraduodenal infusion of glucose increased the concentration of pancreatic polypeptide (PP) in serum from 13.4 (4.0-20.4) to 36.9 (20.7-81.3) pM. Alpha blockade with phentolamine increased the PP concentration from 15.0 (4.0-23.7) to 24.9 (4.6-50.2) pM, and after intraduodenal glucose to 46.8 (23.6-132.8) pM. The PP release after intraduodenal glucose was small, transient, and significantly reduced when beta blockade with propranolol was administered. Oral glucose increased the concentration of PP from 19.3 (4.2-37.0) to 61.1 (14.1-141.7) pM. Isoprenaline increased the PP concentration from 13.5 (4.6-33.8) to 56.0 (5.7-137.3) pM, and after oral glucose to 77.5 (25.3-134.7) pM. The increase in PP concentration was eliminated when propranolol was added to isoprenaline. We conclude that an intestinal phase of PP release exists after intraduodenal glucose in healthy humans, and that the PP release after intraduodenal and oral glucose can be modified by the adrenergic nervous system. Alpha blockade stimulates the PP cell; beta blockade or stimulation respectively inhibits or stimulates the PP cell.