During dynamic exercise, blood flow to exercising muscle is closely matched to metabolic demands. This is made possible by metabolic vasodilation, vasoconstriction in inactive vascular beds, and a rise in cardiac output. The sympathetic nervous system plays an important role in regulating this exercise response. In this study, we used steady-state infusions of tritiated norepinephrine ([3H]NE) to determine the magnitude and time course of the arterial NE spillover response to sustained upright bicycle exercise at low (n = 11) and moderate-to-high (n = 14) exercise intensity (25 and 65% of maximum work load, respectively) in normal young subjects. In addition, we sought to examine whether exercise was associated with a change in NE clearance. During 30 min of low-level exercise, arterial NE spillover increased from 1.45 +/- 0.13 to 3.14 +/- 0.30 nmol.min-1 x m-2 (P < 0.01) and appeared to plateau at 20-30 min of exercise; NE clearance remained unchanged. During 20 min of moderate-to-high-intensity exercise, we found a substantial and progressive rise of arterial NE spillover from 2.15 +/- 0.27 to 13.52 +/- 1.62 nmol.min-1 x m-2 (P < 0.01). NE clearance decreased from 0.91 +/- 0.05 to 0.80 +/- 0.05 l.min-1 x m-2 (P < 0.05). These data suggest that, during dynamic exercise, sympathetic nervous system activity is related to exercise intensity, and there appears to be an interaction between the effects of exercise intensity and duration on NE spillover. In addition, at moderate-to-high exercise intensity, a small decrease of NE clearance contributes to the rise in plasma NE.