The response of whole-body glucose uptake and oxidation and hindlimb glucose and lactate balance was investigated using the hyperinsulinemic, euglycemic clamp in 12 sham-operated control dogs and 10 hepatectomized dogs. A combination of radioactive (NaH14CO3) and stable (U-13C-glucose) isotope tracers was used to quantify glucose kinetics and oxidation. The insulin concentration was increased to approximately 5,000 microU/mL. Mean glucose uptake rates across the hindlimb were similar, 7.72 and 8.06 mumol.kg-1.min-1 for hepatectomy and sham-operated groups, respectively. Lactate release across the hindlimb also showed no significant differences between the two groups. Therefore, it was concluded that the liver did not affect peripheral glucose uptake in response to supramaximal insulin infusion under these experimental conditions. On the other hand, the mean glucose infusion rate during the last 60 minutes of the insulin clamp in the hepatectomy group was significantly decreased compared with that in the sham-operated group, 57.11 versus 46.29 mumol.kg-1.min-1, respectively (P < .05). Consequently, the maximal capacity of the liver of the anesthetized dog to clear glucose in response to supramaximal insulin infusion appears to be approximately 10.8 mumol.kg-1.min-1, which is about 20% of the total glucose infused. Isotopic data showed that most hepatic glucose uptake was oxidized. In contrast, most peripheral glucose uptake appeared to be stored as glycogen.