We studied the effects of maintained hyperglycemia (12 mmol/l) on endurance exercise to determine the hormonal and metabolic responses, the maximal rate of glucose infusion (i.e., utilization), and the effects on muscle glycogen stores. Eight men undertook two trials during which they exercised on a cycle ergometer at an intensity of ~70% peak O₂ uptake for 120 min. In the first trial (trial A), subjects had their blood glucose concentration clamped at 12 mmol/l 30 min before exercise and throughout exercise. The same rate and volume of infusion of saline as had occurred for trial A were used in a placebo trial (trial B). Maintained hyperglycemia resulted in significantly lowered plasma concentrations of nonesterified fatty acid, glycerol, 3-hydroxybutyrate, epinephrine, norepinephrine, and growth hormone (P < 0.001) during exercise, whereas concentrations of plasma insulin were significantly elevated (P < 0.001). Calculations of the rates of total carbohydrate oxidation showed that trial A resulted in significantly higher values when compared with trial B (P < 0.01) and that the maximal rates of glucose infusion varied between 1.33 and 2.78 g/min at 100-120 min. Muscle glycogen concentrations were significantly depleted (P < 0.01) after both trials (trial A, 170.3 µmol/g dry wt decrease; trial B, 206 µmol/g dry wt decrease), although this apparent difference may be accounted for by storage of 22.6 g glucose during the 30-min prime infusion. The results from this study confirm that maintained hyperglycemia attenuates the hormonal response and promotes carbohydrate oxidation and utilization and that muscle glycogen may not be spared.