Based on animal studies, it has been speculated that muscle metabolites sensitize muscle mechanoreceptors, and increase mechanoreceptor mediated muscle sympathetic nerve activity (MSNA). However, this hypothesis has not been directly tested in humans. In this report, we tested the hypothesis that in healthy individuals passive stretch of forearm muscles would evoke significant increases in mean MSNA when muscle metabolite concentrations were increased. In 12 young healthy subjects, MSNA, ECG and blood pressure were recorded. Subjects performed static fatiguing isometric handgrip at 30% maximum voluntary contraction followed by 4 min of post exercise muscle ischemia (PEMI). After 2 min of PEMI, wrist extension (i.e. wrist dorsiflexion) was performed. The static stretch protocol was also performed during: 1) a freely perfused condition; 2) ischemia alone; and 3) PEMI after non-fatiguing exercise. Finally, repetitive short bouts of wrist extension were also performed under freely perfused conditions. This last paradigm evoked transient increases in MSNA, but had no significant effect on mean MSNA over the whole protocol. During the PEMI after fatiguing handgrip, static stretch induced significant increases in MSNA (552 ± 74 to 673 ± 90 units/min, P < 0.01) and mean blood pressure (102 ± 2 to 106 ± 2 mmHg, P < 0.001). Static stretch performed under the other 3 conditions had no significant effects on mean MSNA and blood pressure. The present data verified that in healthy humans mechanoreceptor(s) stimulation evokes significant increases in mean MSNA and blood pressure when muscle metabolite concentrations are increased to above a certain threshold.