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Epinephrine infusion during moderate intensity exercise increases glucose production and uptake. Am J Physiol Endocrinol Metab 278: E949-E957, 2000.--The glucoregulatory response to intense exercise [IE, [is greater than] 80% maximum [0.sub.2] uptake ([Vo.sub.2max])] comprises a marked increment in glucose production ([R.sub.a]) and a lesser increment in glucose uptake ([R.sub.d]), resulting in hyperglycemia. The [R.sub.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.sub.a], this would support an important role for the catecholamines' response in IE. Seven fit male subjects (26 [+ or -] 2 yr, body mass index 23 [+ or -] 0.5 kg/[m.sup.2], [Vo.sub.2max] 65 [+ or -] 5 ml [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1]) underwent 40 min of postabsorptive cycle ergometer exercise (145 [+ or -] 14 W) once without [control (CON)] and once with Epi infusion [EPI (0.1 [micro]g [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1])] from 30 to 40 min. Epi levels reached 9.4 [+ or -] 0.8 nM (20x rest, 10x CON). [R.sub.a] increased ~70% to 3.75 [+ or -] 0.53 in CON but to 8.57 [+ or -] 0.58 mg [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1] in EPI (P [is less than] 0.001). Increments in [R.sub.a] and Epi correlated ([r.sup.2] = 0.923, P [is less than or equal to] 0.01). In EPI, peak [R.sub.d] (5.55 [+ or -] 0.54 vs. 3.38 [+ or -] 0.46 mg [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1], P = 0.006) and glucose metabolic clearance rate (MCR, P = 0.018) were higher. The [R.sub.a]-to-[R.sub.d] imbalance in EPI caused hyperglycemia (7.12 [+ or -] 0.22 vs. 5.59 [+ or -] 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.sub.a] increase. Norepinephrine (~4 X increase at peak) did not differ between EPI and CON. Thus Epi infusion during moderate exercise led to increments in [R.sub.a] and [R.sub.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.sub.d] and MCR during exercise may differ from its effects at rest. glucose turnover; catecholamines; insulin; glucagon