The increase in hepatic glucose production (HGP) that occurs during intense exercise is accompanied by a simultaneous increase in epinephrine, which suggests that epinephrine may be important in regulating HGP. To further investigate this, six trained men were studied twice. The first trial [control (Con)] consisted of 20 min of cycling at 40 ± 1% peak oxygen uptake (V˙o 2 peak) followed by 20 min at 80 ± 2%V˙o 2 peak. During the second trial [epinephrine (Epi)], subjects exercised for 40 min at 41 ± 2%V˙o 2 peak. Epinephrine was infused during the latter 20 min of exercise and resulted in plasma levels similar to those measured during intense exercise in Con. Glucose kinetics were measured using a primed, continuous infusion of [3-3H]glucose. HGP was similar at rest (Con, 11.0 ± 0.5 and Epi, 11.1 ± 0.5 μmol ⋅ kg−1 ⋅ min−1). In Con, HGP increased (P < 0.05) during exercise to 41.0 ± 5.2 μmol ⋅ kg−1 ⋅ min−1at 40 min. In Epi, HGP was similar to Con during the first 20 min of exercise. Epinephrine infusion increased (P < 0.05) HGP to 24.0 ± 2.5 μmol ⋅ kg−1 ⋅ min−1at 40 min, although this was less (P< 0.05) than the value in Con. The results suggest that epinephrine can increase HGP during exercise in trained men; however, epinephrine during intense exercise cannot fully account for the rise in HGP. Other glucoregulatory factors must contribute to the increase in HGP during intense exercise.