There is growing information regarding the role of the nervous system in the regulation of the pathophysiology of the biliary epithelium[3,22-27]. In the liver, adrenergic and cholinergic nerves are located around the hepatic artery, portal vein, and the biliary epithelium[28,29]. The intrahepatic arteries, veins, bile ducts and hepatocytes are also innervated[28,29]. In the autonomic nervous system, there are a number of regulatory peptides including neuropeptide tyrosine (NPY)[30,31], calcitonin gene related peptide (CGRP), somatostatin, vasoactive intestinal polypeptide (VIP) (mostly associated with parasympathetic fibers), enkephalin and bombesin[31-35]. NPY-positive nerves are present in extrahepatic bile ducts and have been suggested to regulate bile flow by autocrine/paracrine mechanisms. We have shown that NPY inhibits cholangiocarcinoma growth by interaction with a G-protein coupled receptor by Ca2+-dependent modulation of Src/ERK1/2 phosphorylation. Nerve fibers containing CGRP and substance P are present around blood vessels and bile duct radicles within portal tracts[39,40]. VIP-positive nerve fibers are located in the walls of hepatic arteries, portal veins and bile ducts.