We sought to examine the potential role of oxidative stress on skeletal muscle function with advancing age. Nuclear magnetic resonance (NMR) was employed to simultaneously assess muscle perfusion (arterial spin labeling) and energetics ((31)P NMR spectroscopy) in the lower leg of young (26 + or - 5 yr, n = 6) and older (70 + or - 5 yr, n = 6) healthy volunteers following the consumption of either placebo (PL) or an oral antioxidant (AO) cocktail (vitamins C and E and alpha-lipoic acid), previously documented to decrease plasma free radical concentration. NMR measurements were made during and after 5 min of moderate intensity (approximately 5 W) plantar flexion exercise. AO administration significantly improved end-exercise perfusion (AO, 50 + or - 5, and PL, 43 + or - 4 ml x 100 g(-1) x min(-1)) and postexercise perfusion area under the curve (AO, 1,286 + or - 236, and PL, 866 + or - 144 ml/100 g) in older subjects, whereas AO administration did not alter hemodynamics in the young group. Concomitantly, muscle oxidative capacity (time constant of phosphocreatine recovery, tau) was improved following AO in the older (AO, 43 + or - 1, and PL, 51 + or - 7 s) but not the young (AO, 54 + or - 5, and PL, 48 + or - 7 s) group. These findings support the concept that oxidative stress may be partially responsible for the age-related decline in skeletal muscle perfusion during physical activity and reveal a muscle metabolic reserve capacity in the elderly that is accessible under conditions of improved perfusion.