This study compared the effects of glucose feeding and water on endurance performance, glycogen utilization, and endocrine responses to exhaustive running in rats. Forty-eight trained rats ran at ~70% peak O2 consumption (Vo2) while receiving, via gavage, 1 ml of an 18% glucose solution or water every 30 min. Glucose (GF) and water-fed rats (WF) were pair matched and killed at rest, at 25 or 50% of their previously determined run time to exhaustion, or at exhaustion. Run times to exhaustion were 4.6 ± 1.0 and 3.0 ± 0.9 h in GF and WF rats, respectively. In WF rats, plasma glucose declined continuously a resting value of 7.4 ± 0.5 to 1.8 ± 0.5 mM at exhaustion and was lower than in GF rats at all exercise time points. In GF rats, glucose was maintained at 7.4 ± 0.5 mM for 3 h before dropping to 3.9 ± 0.6 mM at exhaustion. In both groups, liver and muscle glycogen decreased dramatically during the 1st h and changed only slightly thereafter. During the 3rd h, glycogen levels were maintained in GF rats but continued to decrease in WF rats (P < 0.05). Insulin decreased during exercise and was not significantly different between groups. Glucagon, epinephrine, norepinephrine, and corticosterone increased to a greater extent in WF than in GF rats during the first 3 h of exercise. These results demonstrate a remarkable ability of oral glucose feedings to maintain plasma glucose and presumably supply nearly all the necessary carbohydrate for exercise at this intensity when both liver glycogen and muscle glycogen among all fiber types are very low.