Muscle blood flow increases almost linearly with exercise and reaches peak values at maximal exercise. This is achieved by the combination of a small increase in perfusion pressure and massive vasodilatation. The greatest levels of muscle perfusion have been reported in the quadriceps muscle during knee extension exercise (250-450 ml.min-1.kg-1) (Andersen & Saltin, 1985; Blomstrand et al., 2011). A singularity of this exercise model is that the amount of muscle activated (about 2.5-3 kg) is small and, therefore, the pumping capacity of the heart is not taxed. Endurance training and high-intensity intermittent knee extension training increases maximal exercise vasodilatation by 20-30% mainly due to enhanced vasodilatory capacity, inasmuch as maximal exercise perfusion pressure changes little with training. However, part of the increase in maximal exercise oxygen conductance is explained by muscle hypertrophy (Blomstrand et al., 2011). Maximal exercise vasodilatation results from the balance between vasoconstricting and vasodilating signals combined with the vascular reactivity to these signals. In young healthy humans the muscles that are activated are also fully vasodilatated during small muscle mass exercise (Ray & Dudley, 1998). The infusion of potent vasodilators fails to increase total limb perfusion but alters blood flow distribution and O2M extraction at the microvascular level. The muscle areas less metabolically active are less vasodilatated and, hence, are more sensitive to an intra-arterially infused vadodilator. Consequently, some blood flow is deviated to areas with lower oxygen demand and the O2M extraction is diminished (Heinonen et al., 2010). Maximal exercise vasodilatory capacity is reduced or blunted with ageing, as well as in chronic heart failure patients and chronically hypoxic humans; reduced vasodilatory responsiveness and increased sympathetic activity are potential mechanisms accounting for this effect. During maximal whole body exercise maximal vasodilatation is restrained by the sympathetic system. This is necessary to avoid hypotension since the maximal vascular conductance of the musculature exceeds the maximal pumping capacity of the heart (Calbet et al., 2004). Pharmacological counteraction of the sympathetic restraint may result in lower perfusion pressure and reduced oxygen extraction by the exercising muscles during whole body exercise (Calbet et al., 2006; Lundby et al., 2008). However, fast inhibition of the chemoreflex in maximally exercising humans may result in increased vasodilation (Stickland et al., 2011), further confirming a restraining role of the sympathetic nervous system on maximal exercise-induced vasodilatation. This vasoconstriction by the sympathetic system is likely critical for the maintenance of blood pressure in exercising patients with a limited heart pump.