In vivo microdialysis was applied to investigate the effects of hepatic nerve stimulation on glycogenolysis in rat liver under anesthesia. We analyzed the norepinephrine (NE) outflow and glucose output from the liver through the measurement of NE and glucose in the microdialysis dialyzate, as well as the plasma glucose level. Stimulation of the hepatic nerves (10 Hz, 20 V, 2 ms, 20 s every minute) increased NE outflow and glucose output from the liver. The blood glucose level increased by 1.5-1.6 times over the basal level at the end of the 10 min intermittent stimulation. Bilateral adrenalectomy and pancreatectomy did not abolish the glycogenolysis that was induced by the nerve stimulation. Phentolamine an alpha-antagonist, reduced the effects of nerve stimulation on the glucose output and the plasma glucose level. Phentolamine caused an increase in the NE outflow. Quinacline, an inhibitor of phospholipase A2, inhibited the glycogenolytic nerve effects without any inhibition of the NE outflow. These data show that hepatic nerve stimulation produces glycogenolysis via alpha-adrenergic mechanism and partly mediated by eicosanoids, and that microdialysis is a useful and simple method for the study of liver metabolism in physiological conditions.