This study examined the effect of combined α- and β-adrenergic blockade on glucose kinetics during intense exercise. Six endurance-trained men exercised for 20 minutes at approximately 78% of their peak oxygen consumption (Vo2) following ingestion of a placebo (CON) or combined α- (prazosin hydrochloride) and β- (timolol maleate) adrenoceptor antagonists (BLK). Plasma glucose increased during exercise in CON (0 minutes: 5.5 ± 0.1; 20 minutes: 6.5 ± 0.3 mmol.L-1, P < .05). In BLK, the exercise-induced increase in plasma glucose was abolished (0 minutes: 5.7 ± 0.3; 20 minutes: 5.7 ± 0.1 mmol.L-1). Glucose kinetics were measured using a primed, continuous infusion of [6,6-2H] glucose. Glucose production was not different between trials; on average these values were 25.3 ± 3.9 and 30.9 ± 4.4 μmol.kg-1.min-1 in CON and BLK, respectively. Glucose uptake during exercise was greater (P < .05) in BLK (30.6 ± 4.6 μmol.kg-1.min-1) compared with CON (18.4 ± 2.5 μmol.kg-1.min-1). In BLK, plasma insulin and catecholamines were higher (P < .05), while plasma glucagon was unchanged from CON. Free fatty acids (FFA) and glycerol were lower (P < .05) in BLK. These findings demonstrate that adrenergic blockade during intense exercise results in a blunted plasma glucose response that is due to enhanced glucose uptake, with no significant change in glucose production.