In perfused rat liver perivascular nerve stimulation (7.5 Hz, 20 V, 2 ms, 5 min) at the liver hilus caused an increase in glucose release, a shift of lactate uptake to output and a decrease in arterial, portal and total flow. The influence of the alpha 1-receptor blocker prazosin and the beta-antagonist propranolol on these nerve effects were studied in the isolated rat liver perfused via both the hepatic artery and the portal vein in three experimental series at 9 a.m., at 2 p.m. and at 8 p.m. 1) The nerve stimulation-dependent increase in glucose output was maximal at 9 a.m. (100%), halfmaximal at 2 p.m. (50%) and very low at 8 p.m. (15%). The alterations in arterial, portal and total flow were similar in all three series. 2) At 9 a.m., at 2 p.m. and at 8 p.m. 5 microM arterial plus portal prazosin nearly completely inhibited the metabolic alterations and blocked the reduction of arterial, portal and total flow by 80%. 3) At 9 a.m. 10 microM arterial, portal and arterial plus portal propranolol inhibited the increase in glucose release to less than 25% and the shift of lactate uptake to output to about 50%. At 2 p.m. this inhibitory effect was not observed, neither by selective arterial or portal, nor by simultaneous arterial plus portal addition of 10 microM propranolol. At 8 p.m. the influence of propranolol could not be studied because of the too small control values. The nerve stimulation-dependent reduction of arterial, portal and total flow was not influenced by propranolol, neither at 9 a.m. nor at 2 p.m.(ABSTRACT TRUNCATED AT 250 WORDS)