Perivascular nerve stimulation of rat livers perfused in situ with erythrocyte-free Krebs-Henseleit buffer at constant pressure in a non-reci/'culating system resulted in an increase of glucose and lactate production and in a decrease of portal flow. Infusion of somatostatin in different concentrations (2 x 10 '7, 10 -8, 10 -9 mol.1-1 ) reduced the nerve-mediated activation of glucose releasemaximally to 66%. There was only a slight effect on the lactate output, the nerve-mediated reduction of portal flow was unaltered. In controls, somatostatin alone had no effect on the metabolic and hemodynamic parameters. In order to differentiate between a presynaptic and postsynaptic mechanism, the noradrenaline overflow was calculated. The unaltered release of the neurotransmitter in the presence or absence of somatostatin excluded a presynaptic mechanism. To mimic the nerve effects on the carbohydrate metabolism and on the hemodynamics, noradrenaline (2 x 10 -7. mol-1-1) was infused instead of the nerve stimulation over a period of 5 min. Somatostatin did not change the endocrine effects of the eatecholamine under these conditions. The nerve-dependent effect of somatostatin suggests that other neurotransmitters (e.g. VIP) or mediators (e.g. prostanoids) may be influenced by somatostatin.