Sympathetic vasoconstrictor responses are blunted in the vascular beds of contracting muscle (functional sympatholysis), but the mechanism(s) have been difficult to elucidate. We tested the hypothesis that the mechanical effects of muscle contraction blunt sympathetic vasoconstriction in human muscle. We measured forearm blood flow (Doppler ultrasound) and calculated the reductions in forearm vascular conductance (FVC) in response to reflex increases in sympathetic activity evoked via lower body negative pressure (LBNP). In Protocol 1, 8 young adults were studied under control resting conditions and during simulated muscle contractions using rhythmic forearm cuff inflations (20 inflations/min) with cuff pressures of 50 and 100 mmHg with the arm below heart level (BH), as well as 100 mmHg with the arm at heart level (HL). Forearm vasoconstrictor responses (% FVC) during LBNP were -26±2 % during control conditions, and were not blunted by simulated contractions (range = -31±3% to -43±6%). In Protocol 2, 8 subjects were studied under control conditions and during rhythmic handgrip exercise (20 contractions/min) using workloads of 15% maximum voluntary contraction (MVC) at HL and BH (similar metabolic demand, greater mechanical muscle pump effect for the latter) and 5% MVC BH alone and in combination with superimposed forearm compressions of 100 mmHg (similar metabolic demand, greater mechanical component of contractions for the latter). The forearm vasoconstrictor responses during LBNP were blunted during 15% MVC exercise with the arm at HL (-1±3%) and BH (-2±3%) compared with control (-25±3%; both P<0.005), but were intact during both 5% MVC alone (-24±4%) and with superimposed compressions (-23±4%). We conclude that mechanical effects of contraction per se do not cause functional sympatholyis in the human forearm, and that this phenomenon appears to be coupled with the metabolic demand of contracting skeletal muscle.