1. The effects of 50- and 100-g glucose loads on carbohydrate and lipid oxidation and substrate metabolism of seven normal subjects were studied in the postabsorptive state and for 3 h following glucose ingestion. 2. The increases in the non-protein respiratory quotient (npRQ) and carbohydrate oxidation rate were larger after the ingestion of 100 g glucose than after the 50-g glucose load. The total amount of glucose oxidized during the test with 100 g of glucose ingested orally (100-g OGT) (13.4 +/- 0.8 g/m2) was significantly greater than that oxidized during the 50-g OGT (9.5 +/- 0.6 g/m2), whereas lipid oxidation predominated in the tests with the smaller dose of glucose. The difference between the amounts of glucose oxidized during the two tests was greater when the increments above the basal values of glucose oxidation were compared (100-g OGT = 8.0 +/- 0.5 g/m2 vs 50-g OGT = 3.8 +/- 0.5 g/m2; P less than 0.001). 3. The glucose disposal data revealed that the subjects not only oxidized more of the hexose after the ingestion of 100 g of glucose but they also stored more than after the 50-g glucose meal. 4. The changes in the concentrations of glucose, lactate, pyruvate, alanine and insulin in the blood were also related to the amount of the glucose load. 5. It is suggested that the modulation of this oxidative response to glucose ingestion occurs in the insulin-dependent tissues.