To characterize postprandial glucose disposal more completely, we used the tritiated water technique, a triple-isotope approach (intravenous [3-H³]glucose and [¹⁴C]bicarbonate and oral [6,6-²H₂]glucose) and indirect calorimetry to assess splanchnic and peripheral glucose disposal, direct and indirect glucose storage, oxidative and nonoxidative glycolysis, and the glucose entering plasma via gluconeogenesis after ingestion of a meal in 11 normal volunteers. During a 6-h postprandial period, a total of ∼98 g of glucose were disposed of. This was more than the glucose contained in the meal (∼78 g) due to persistent endogenous glucose release (∼21 g): splanchnic tissues initially took up ∼23 g, and an additional ∼75 g were removed from the systemic circulation. Direct glucose storage accounted for ∼32 g and glycolysis for ∼66 g (oxidative ∼43 g and nonoxidative ∼23 g). About 11 g of glucose appeared in plasma as a result of gluconeogenesis. If these carbons were wholly from glucose undergoing glycolysis, only ∼12 g would be available for indirect pathway glycogen formation. Our results thus indicate that glycolysis is the main initial postprandial fate of glucose, accounting for ∼66% of overall disposal; oxidation and storage each account for ∼45%. The majority of glycogen is formed via the direct pathway (∼73%).