We examined the role of efferent neural signaling in regulation of net hepatic glucose uptake (NHGU) in two groups of conscious dogs with hollow perfusable coils around their vagus nerves, using tracer and arteriovenous difference techniques. Somatostatin; intraportal insulin and glucagon at 4-fold basal and basal rates, respectively; and intraportal glucose at 3.8 mg^.kg^-1.min^-1 were infused continuously. From 0-90 min (period 1 [P1]), the coils were perfused with a 37°C solution. During P2 (90-150 min in group 1 [n=3]; 90-180 min in group 2 [n=6]), the coils were perfused with -15°C solution to eliminate vagal signaling, and the coils were subsequently perfused with 37°C solution during P3. In addition, group 2 received an intraportal infusion of norepinephrine at 16 ng^.kg^-1.min^-1 during P2. The effectiveness of vagal suppression was demonstrated by the increase in heart rate during P2 (111±17, 167±16, and 105±13 bpm in group 1 and 71±6, 200±11, and 76±6 bpm in group 2 during P1-P3, respectively) and by prolapse of the 3rd eyelid during P2. Arterial plasma glucose, insulin, and glucagon concentrations; hepatic blood flow; and hepatic glucose load did not change significantly during P1-P3. NHGU during P1-P3 was was 2.7±0.4, 4.1±0.6, and 4.0±1.2 mg^.kg^-1. min^-1 in group 1 and 5.0±0.9, 5.6±0.7, and 6.3±1.0 mg^.kg^-1.min^-1 in group 2 (NS among periods). Interruption of vagal signaling with or without intraportal infusion of norepinephrine to augment sympathetic tone did not suppress NHGU during portal glucose delivery, suggesting the portal signal stimulates net hepatic glucose uptake independently of vagal efferent flow.