The glucoregulatory response to intense exercise [IE, >80% maximum O(2) uptake (VO(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/m(2), VO(2 max) 65 +/- 5 ml x kg(-1) x min(-1)) underwent 40 min of postabsorptive cycle ergometer exercise (145 +/- 14 W) once without [control (CON)] and once with Epi infusion [EPI (0.1 microg x kg(-1) x min(-1))] from 30 to 40 min. Epi levels reached 9.4 +/- 0.8 nM (20x rest, 10x CON). R(a) increased approximately 70% to 3.75 +/- 0.53 in CON but to 8.57 +/- 0.58 mg x kg(-1) x min(-1) in EPI (P < 0.001). Increments in R(a) and Epi correlated (r(2) = 0.923, P </= 0.01). In EPI, peak R(d) (5.55 +/- 0.54 vs. 3.38 +/- 0.46 mg x kg(-1) x min(-1), 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 (approximately 4x 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.