The consequences of autonomic diabetic neuropathy, a common complication of chronic diabetes mellitus, have been studied mainly with regard to heart and stomach function. Since the autonomic nervous system also regulates liver carbohydrate metabolism and haemodynamics via hepatic nerves, it was the purpose of this study to examine the function of hepatic nerves in chronically diabetic rats. Diabetes was induced by i.p. injection of streptozotocin. Rat livers were perfused via both portal vein and hepatic artery. Hepatic nerves were stimulated for 2 min using a platinum electrode placed around the portal vein and the hepatic artery; in an additional stimulation phase noradrenaline was infused into the portal vein. Stimulation of hepatic nerves as well as portal noradrenaline infusion increased hepatic glucose output and reduced flow in control and in acutely (48-h) diabetic animals, which still had almost normal glycogen content. In addition stimulation also caused an overflow of noradrenaline into the caval vein. However, nerve stimulation neither increased glucose output nor decreased flow in 4-month diabetic rats. In these rats noradrenaline overflow was nearly completely abolished and hepatic glycogen content was markedly depleted. Portal noradrenaline infusion in chronically diabetic rats reduced flow to a similar extent as in controls, yet the increase in glucose output was diminished. The lack of nerve stimulation-dependent glucose output, flow reduction and noradrenaline overflow is indicative of a profound loss of function of hepatic autonomic nerves in chronically diabetic rats.