The effects of exercise on the distensibility of large and medium-sized arteries are poorly understood, but can be attributed to a combination of local vasodilator effects of exercise opposed by sympathetic vasoconstrictor tone. We sought to examine this relationship at the conduit artery level, with particular reference to the role of the sympatho-excitatory muscle metaboreflex. The effect of maintained muscle metaboreflex activation on a previously passive or exercised limb femoral artery was investigated. A total of ten healthy volunteers performed 2 min of isometric ankle plantar-flexion at 40% MVC (maximal voluntary force), in conjunction with 2 min of either non-ischaemic isometric HG (handgrip; control condition) or IHG (ischaemic HG) at 40% MVC. IHG was followed by 2 min of PECO (post-exercise circulatory occlusion) to maintain muscle metaboreflex activation. FTPWV [femoral–tibial PWV (pulse wave velocity)] was measured in the exercised or contralateral limb at baseline and immediately following calf exercise. BP (blood pressure) and HR (heart rate) were measured continuously throughout. In the HG condition, BP and HR returned promptly to baseline post-exercise, whereas exercised leg FTPWV was decreased (less stiff) by 0.6 m/s ( P <0.05) and the non-exercised leg PWV was not changed from baseline. PECO caused a sustained increase in BP, but not HR, in the IHG condition. Contralateral leg PWV increased (stiffened) during PECO by 0.9 m/s ( P <0.05), whereas exercised limb FTPWV was not changed from baseline. In conclusion, muscle metaboreflex activation causes a systemic stiffening of the arterial tree, which can overcome local exercise-induced decreases in arterial PWV.