The glucoregulatory response to intense exercise [IE, >80% maximum O₂ uptake (O_{2 max})] comprises a marked increment in glucose production (R_a) and a lesser increment in glucose uptake (R_d), resulting in hyperglycemia. The R_a correlates with plasma catecholamines but not with the glucagon-to-insulin (IRG/IRI) ratio. If epinephrine (Epi) infusion during moderate exercise were able to markedly stimulate R_a, this would support an important role for the catecholamines' response in IE. Seven fit male subjects (26 ± 2 yr, body mass index 23 ± 0.5 kg/m², O_{2 max} 65 ± 5 ml · kg¹ · min¹) underwent 40 min of postabsorptive cycle ergometer exercise (145 ± 14 W) once without [control (CON)] and once with Epi infusion [EPI (0.1 µg · kg¹ · min¹)] from 30 to 40 min. Epi levels reached 9.4 ± 0.8 nM (20× rest, 10× CON). R_a increased ~70% to 3.75 ± 0.53 in CON but to 8.57 ± 0.58 mg · kg¹ · min¹ in EPI (P < 0.001). Increments in R_a and Epi correlated (r² = 0.923, P  0.01). In EPI, peak R_d (5.55 ± 0.54 vs. 3.38 ± 0.46 mg · kg¹ · min¹, P = 0.006) and glucose metabolic clearance rate (MCR, P = 0.018) were higher. The R_a-to-R_d imbalance in EPI caused hyperglycemia (7.12 ± 0.22 vs. 5.59 ± 0.22 mM, P = 0.001) until minute 60 of recovery. A small and late IRG/IRI increase (P = 0.015 vs. CON) could not account for the R_a increase. Norepinephrine (~4× increase at peak) did not differ between EPI and CON. Thus Epi infusion during moderate exercise led to increments in R_a and R_d and caused rises of plasma glucose, lactate, and respiratory exchange ratio in fit individuals, supporting a regulatory role for Epi in IE. Epi's effects on R_d and MCR during exercise may differ from its effects at rest.