Pancreatic endocrine responses to vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating peptide (PACAP) and acetylcholine have been investigated in conscious calves, while continuously monitoring aortic blood pressure and heart rate, in order to assess the effects of these neuropeptides under normal physiological conditions. VIP was found to modulate the release of pancreatic polypeptide (PP) in response to acetylcholine at a dose which had no significant effect on the release of either pancreatic glucagon or insulin. PACAP stimulated the release of insulin and the effect was potentiated during infusions of exogenous glucose. PACAP, when infused together with acetylcholine, also stimulated the release of pancreatic glucagon in the absence of exogenous glucose but not in its presence. Release of PP was stimulated during infusions of PACAP, whether or not exogenous glucose was given, and this effect was found to be additive with that of acetylcholine.