Obstructive cardiovascular disease decelerates the on-kinetics of the body's oxygen uptake rate (VO2), either by reducing the O2 delivery or by degrading the exercise capacity of skeletal muscle. This study sought to determine whether obstructed blood flow decelerates the on-kinetics of VO2 by reducing O2 delivery. Breath-by-breath measurements of VO2 were studied in eight healthy youth (age, 16.5 +/- 0.6 years) during two-legged square-wave exercise on the cycle ergometer. The square protocol was 5 minutes of unloaded exercise followed by an immediate increase to 5 minutes of loaded exercise at 78 +/- 5 W. In the experimental trials, thigh cuffs were inflated 30 seconds before the onset of loaded exercise. Control trials replicated the square-wave exercise with deflated thigh cuffs. The on-kinetics of VO2 were biphasic in the control trial and triphasic in the experimental trial. Experimental VO2 was significantly higher than control values in the final 90 seconds of exercise (P<.05). The difference between experimental and control VO2 was attributable to inflated thigh cuffs. At no time was experimental VO2 significantly lower than control VO2. The clinical implication of the results is that skeletal myopathy, not reduced blood flow, is essential for decelerating the VO2 on-kinetics of patients with obstructive vascular disease. The warranted conclusion is that square-wave exercise with inflated thigh cuffs stimulates a third phase of VO2 on-kinetics.