The present study investigated potential sex-related differences in the metabolic response to carbohydrate (CHO) ingestion during exercise. Moderately endurance-trained men and women (n ϭ 8 for each sex) performed 2 h of cycling at ϳ67% V O2 max with water (WAT) or CHO ingestion (1.5 g of glucose/min). Substrate oxidation and kinetics were quantified during exercise using indirect calorimetry and stable isotope techniques ([ 13 C]glucose ingestion, [6,6-2 H2]glucose, and [ 2 H5]glycerol infusion). In both sexes, CHO ingestion significantly increased the rates of appearance (R a) and disappearance (Rd) of glucose during exercise compared with WAT ingestion [males: WAT, ϳ28 -29 mol ⅐ kg lean body mass (LBM); main effect of trial, P Ͻ 0.05]. The contribution of plasma glucose oxidation to the energy yield was significantly increased with CHO ingestion in both sexes (from ϳ10% to ϳ20% of energy expenditure; main effect of trial, P Ͻ 0.05). Liver-derived glucose oxidation was reduced, although the rate of muscle glycogen oxidation was unaffected with CHO ingestion (males: WAT, 108. CHO ingestion reduced fat oxidation and lipolytic rate (Ra glycerol) to a similar extent in both sexes. Finally, ingested CHO was oxidized at similar rates in men and women during exercise (peak rates of 0.70 Ϯ 0.08 and 0.65 Ϯ 0.06 g/min, respectively). The present investigation suggests that the metabolic response to CHO ingestion during exercise is largely similar in men and women. stable isotopes; substrate utilization; glucose ingestion; sex-related differences THE INFLUENCE OF SEX-RELATED DIFFERENCES on the metabolic response to exercise has received considerable interest in the last 10 -15 years. The majority of well-controlled studies indicate that, compared with men, women rely more on fat and less on carbohydrate (CHO) oxidation during aerobic exercise performed at the same relative intensity (for reviews, see Refs. 31 and 33). Sex-related differences in the metabolic response to exercise could have implications for nutritional recommendations and athletic performance for male and female athletes (30,32). In this respect, the metabolic and performance responses to the ingestion of CHO during exercise have been investigated over the last 25 years (for review, see Ref. 18), although the extent to which sex directly influences these responses has not been comprehensively studied.CHO supplementation during exercise increases endurance exercise capacity and performance in males and females (1,2,5,6,8,9). This effect is largely attributed to increased CHO oxidation and maintenance of euglycemia during exercise, particularly as exercise duration increases and endogenous CHO stores become low (6,8). Studies using isotope dilution techniques have shown that glucose turnover, as measured by the rates of appearance and disappearance of glucose (R a and R d glucose), is increased in both sexes when CHO is ingested during exercise (3,5,20,21,24). In addition, in men (3,20,21,24) and women (5), CHO ingestion during exercise reduces and replaces...