The mechanisms underlying metabolic inhibition of sympathetic responses within exercising skeletal muscle remain incompletely understood. The aim of the present study was to test whether ₂- adrenoreceptor-mediated vasoconstriction was more sensitive to metabolic inhibition than ₁- vasoconstriction during dynamic knee-extensor exercise. We studied healthy volunteers using two protocols: 1) Wide dose-ranges of the -adrenoreceptor agonists phenylephrine (PE, ₁ selective) and BHT-933 (BHT, ₂ selective) were administered intra-arterially at rest and during 27W knee-extensor exercise (n=13); 2) Flow-adjusted doses of PE (0.3 µg.kg^-1.l^-1.min^-2) and BHT (15 µg.kg^-1.l^-1.min^-2) were administered at rest and during ramped exercise (7W-37W) (n=10). Ultrasound Doppler and thermodilution techniques provided direct measurements of femoral blood flow (FBF). PE (0.8 µg.kg^-1.min^-1) and BHT (40 µg.kg^-1.min^-1) produced comparable maximal reductions in FBF at rest (-58±6 vs. -64±4%). Despite increasing the doses, PE (1.6 µg.kg^-1.min^-1) and BHT (80 µg.kg^-1.min^-1) caused significantly smaller changes in FBF during 27W-exercise (-13±4 vs. -3±5%). During ramped exercise, significant vasoconstriction at lower intensities (7 and 17W) was seen following PE (-16±5 and -16±4%), but not BHT (-2±4 and -4±5%). At the highest intensity (37W), FBF was not significantly changed by either drug. Collectively, these data demonstrate metabolic inhibition of -adrenergic vasoconstriction in large postural muscles of healthy humans. Both ₁- and ₂-adrenoreceptor agonists produce comparable vasoconstriction in the resting leg, and dynamic thigh exercise attenuates ₁- and ₂-mediated vasoconstriction similarly. However, ₂-mediated vasoconstriction appears more sensitive to metabolic inhibition, because ₂ is completely inhibited even at low workloads, whereas ₁ becomes progressively inhibited with increasing workloads.