To determine whether the uptake and metabolic partition of glucose are influenced by its delivery route, 12 normal volunteers underwent two 3-hour euglycemic (~93 mg/dl) hyperinsulinemic (~43 mU/l) clamps at a 3-5-wk interval, one with intravenous (iv) and the other with intraduodenal (id) glucose labeled with [3-³H]- and [U-¹⁴C] glucose. Systemic glucose was traced with [6,6-²H₂] glucose in 8 subjects. During the last hour of the clamps, the average glucose infusion rate (5.85±0.37 vs 5.43±0.43 mg.kg^-1.min^-1; P=0.02) and exogenous glucose uptake (5.66±0.37 vs 5.26±0.41 mg.kg^-1.min^-1; P=0.04) were borderline higher in the id than iv studies. The increased uptake was entirely accounted for by increased glycolysis (³H₂O production) which was attributed to the stimulation of gut metabolism by the absorptive process. No difference was observed in glucose storage wether it was calculated as glucose uptake - glycolysis (id vs iv: 2.44±0.28 vs 2.40±0.31 mg.kg^-1.min^-1) or as glucose uptake - net glucose oxidation (2.86±0.33 vs 2.81±0.35 mg.kg^-1.min^-1). Because peripheral tissues were exposed to identical glucose, insulin and free fatty acid levels under the two experimental conditions, we assumed that their glucose uptake and storage were similar during the two tests. We therefore suggest that hepatic glycogen storage (estimated as whole body minus peripheral storage) was also unaffected by the route of glucose delivery. On the other hand, in the id tests, the glucose splanchnic extraction ratio calculated by the dual isotope technique averaged 4.9±2.3%, which is close to the figures published for iv glucose. Despite the limitations related to whole body measurements, these two sets of data do not support the idea that enteral glucose stimulates hepatic uptake more efficiently than iv glucose.