This study determined the effects of elevated plasma epinephrine on fat metabolism during exercise. On four occasions, seven moderately trained subjects cycled at 25% of peak oxygen consumption (VO(2 peak)) for 60 min. After 15 min of exercise, subjects were intravenously infused with low (0.96 +/- 0.10 nM), moderate (1.92 +/- 0.24 nM), or high (3.44 +/- 0.50 nM) levels (all P < 0.05) of epinephrine to increase plasma epinephrine above control (Con; 0.59 +/- 0.10 nM). During the interval between 35 and 55 min of exercise, lipolysis [i.e., rate of appearance of glycerol] increased above Con (4.9 +/- 0.5 micromol. kg(-1). min(-1)) with low, moderate, and high (6.5 +/- 0.5, 7.1 +/- 0.8, and 10.6 +/- 1.2 micromol. kg(-1). min(-1), respectively; all P < 0.05) levels of epinephrine despite simultaneous increases in plasma insulin. The release of fatty acid into plasma also increased progressively with the graded epinephrine infusions. However, fatty acid oxidation was lower than Con (11.1 +/- 0.8 micromol. kg(-1). min(-1)) during moderate and high levels (8.7 +/- 0.7 and 8.1 +/- 0.9 micromol. kg(-1). min(-1), respectively; P < 0.05). In one additional trial, the same subjects exercised at 45% VO(2 peak) without epinephrine infusion, which produced a plasma epinephrine concentration identical to low levels. However, lipolysis was lower (i.e., 5.5 +/- 0.6 vs. 6.5 +/- 0.5 micromol. kg(-1). min(-1); P < 0.05). In conclusion, elevations in plasma epinephrine concentration during exercise at 25% of VO(2 peak) progressively increase whole body lipolysis but decrease fatty acid oxidation. Last, increasing exercise intensity from 25 to 45% VO(2 peak) attenuates the lipolytic actions of epinephrine.