Many reports have shown that vagal neural efferent pathways affect the secrtion of insulin and glucagon. However, afferent pathways that might affect this system have received little attention. The present study was carried out to examine the role of the hepatic branch of the vagus nerve, which is composed mostly of afferent fibers in the rat and is a major afferent pathway between the liver and the medulla, in the secretion of insulin and glucagon after the intraperitoneal injection of arginine (1g/kg body weight) in rats. Measurements were made one week after section of this branch. Intraperitoneal arginine enhanced both plasma insulin and glucagon concentrations more in hepatic-vagotomized than in sham-vagotomized rats. The results suggest that inhibition of the secretion of insulin and glucagon after arginine stimulation is mediated by the hepatic branch of the vagus nerve. The existence of “sensors” in the liver for arginine is proposed as an explanation for the inhibition of the secretion of insulin and glucagon by the hepatic vagus nerve.