Using "naturally labeled 13C-glucose" the conversion to expired air CO2 of 100, 66 and 33 g oral glucose loads was evaluated, during 7 hr, in 6 male healthy volunteers. The total amounts of exogenous glucose converted to expired air CO2 were proportional to the loading doses and averaged, in g/7 hr, 14.6 +/- 2.1 for 33 g, 20.8 +/- 2.1 for 66 g and 31.2 +/- 1.6 for 100 g. In contrast total glucose oxidation, evaluated by indirect calorimetry, was similar in the three groups and was not correlated with the dose of glucose given. The plasma insulin response was significantly correlated with the load of glucose (r = 0.86; p less than 0.001) whereas such correlation was not observed with the blood glucose response. Comparison with data available in the literature on the influence of the size of the oral glucose load on endogenous glucose production and on splanchnic glucose output suggests that the greater oxidation of exogenous glucose seen when the oral load of glucose is increased essentially results from a greater enrichment of the systemic glucose pool with exogenous glucose.