The physiological aging process is associated with endothelial dysfunction, as assessed by flow-mediated dilation (FMD). Aging is also characterized by increased sympathetic tone. Therefore, the aim of the present study is to assess whether acute changes in sympathetic activity alter FMD in the leg. Methods. For this purpose, the FMD of the superficial femoral artery was determined in 10 healthy young (22± years) and 8 healthy older (69±1 years) men in three different conditions; 1) at baseline, 2) during reduction of sympathetic activity, and 3) during sympathetic stimulation. Reduction of sympathetic activity was achieved by performing a maximal cycling exercise, leading to post-exercise attenuation of the sympathetic responsiveness in the exercised limb. A cold pressor test was used to increase sympathetic activity. Nitroglycerine (NTG) was used to assess endothelium-independent vasodilation in all 3 conditions. Results. In older men, the FMD and NTG responses were significantly lower compared with young men (P=0.001 and P=0.02, resp.). In older men, sympathetic activity significantly affected the FMD response (RM-ANOVA: P=0.01), with a negative correlation between the level of sympathetic activity and FMD (R=-0.41, P=0.049). This was not the case for the NTG-responses (ANOVA; P=0.48). FMD and NTG responses in young men did not differ between the 3 conditions (RM-ANOVA: P=0.32 and P=0.31, resp.). Conclusions. In older men, FMD of the femoral artery is impaired. Local attenuation of the sympathetic responsiveness partly restores the FMD in these subjects. In contrast, in young subjects acute modulation of the sympathetic nervous system activity does not alter flow-mediated vasodilation in the leg.