Oral glucose (92 g) was administered to 22 healthy, young volunteers undergoing hepatic vein catheterization, and net splanchnic glucose output (SGO) was measured during the basal period and for 4 h after glucose ingestion. In the basal state, SGO averaged 1.90 +/- 0.11 mg/min X kg. After glucose, SGO rose to a peak value of 6.65 +/- 0.83 mg/min X kg at 30 min and returned to baseline by 3 h. Total SGO over 4 h was 69 +/- 4 g; assuming complete absorption of the load, this amount represented 75% of the oral glucose. In a subgroup of six subjects, leg glucose uptake was simultaneously quantitated by femoral vein catheterization and leg blood flow measurement. In the postabsorptive state, glucose uptake by one leg was 24 +/- 8 mg/min and increased to a mean value of 76 +/- 7 mg/min during the 4 h after glucose ingestion. Overall, 18 +/- 2 g/4 h of glucose were taken up by one leg, which extrapolates to a total body muscle uptake of 65 +/- 4 g over 4 h. We conclude that in normal man, well over 2/3 of an oral glucose load escapes splanchnic removal, and that the peripheral tissues quantitatively play the dominant role in glucose disposal.