This study was undertaken to determine the impact of portal adrenergic blockade on the gluconeogenic effects of epinephrine (EPI) and norepinephrine (NE). Experiments were performed on 18-hour fasted conscious dogs and consisted of a 100-minute equilibration, a 40-minute basal, and two 90-minute test periods. A pancreatic clamp was used to fix insulin and glucagon levels at basal values. Propranolol (1 microgram/kg.min) and phentolamine (2 micrograms/kg.min) were infused intraportally during both test periods. Portal infusion of alpha- and beta-adrenergic blockers alone (first test period) slightly increased hepatic glucose production from 2.4 +/- 0.4 to 2.8 +/- 0.5 mg/kg.min (nonsignificant [NS]) NE (500 ng/kg.min) and EPI (180 ng/kg.min) were infused peripherally during the second test period. Arterial NE and EPI increased from 186 +/- 63 to 6,725 +/- 913 pg/mL and 76 +/- 25 to 2,674 +/- 344 pg/mL, respectively. Portal NE and EPI increased from 135 +/- 32 to 4,082 +/- 747 pg/mL and 28 +/- 8 to 1,114 +/- 174 pg/mL, respectively. Hepatic glucose production, the maximal gluconeogenic rate, and gluconeogenic efficiency increased from 2.8 +/- 0.5 to 3.8 +/- 0.4 mg/kg.min (P < .05), 0.7 +/- 0.3 to 2.1 +/- 0.6 mg/kg.min (P < .05), and 21% +/- 8% to 60% +/- 13% (P < .05), respectively, in response to catecholamine infusion. Net hepatic lactate balance changed from output (1.5 +/- 3.3 mumol/kg.min) to uptake (-11.0 +/- 3.8 mumol/kg.min, P < .05). Net hepatic glycerol uptake increased from -1.5 +/- 0.7 to -5.5 +/- 2.0 mumol/kg.min (P < .05). Net hepatic uptake of gluconeogenic amino acids did not change significantly. Similarly, hepatic glycogenolysis did not increase during catecholamine infusion. In conclusion, portal delivery of adrenergic blockers selectively inhibits the glycogenolytic effects of EPI and NE on the liver, but allows a marked gluconeogenic response to the catecholamines.