Increases in plasma noradrenaline (NA) concentration occur during moderate to heavy exercise in man. This study was undertaken to examine the spillover of NA from both resting and contracting skeletal muscle during exercise. Six male subjects performed one-legged knee-extension so that all measurements could be made both in the exercising and in the resting leg. Subjects exercised for 10 min at each of 50% and 100% of the peak performance capacity of the leg. Leg blood flow was measured by thermodilution and blood samples were drawn for the determination of plasma NA and adrenaline, first in the resting leg and then in the exercising leg. To calculate NA spillover, the extraction of NA (NAe) or of adrenalin (Ae) is required: NAe was measured by repeating the experiment under constant [3H]NA infusion following a 40-min rest period. During exercise, NA spillover was significantly larger in the exercising leg than in the resting leg both during 50% and 100% leg exercise. These results suggest that contracting skeletal muscle may contribute to a larger extent than resting skeletal muscle to increasing the level of plasma NA during exercise. Contractile activity may influence the NA spillover from skeletal muscle by a presynaptic and/or postsynaptic influence on the sympathetic nervous activity to this tissue.