Slowed pulmonary O(2) uptake (Vo(2)) kinetics in peripheral arterial disease (PAD) have been attributed to impaired limb blood flow and/or peripheral muscle metabolic abnormalities. Although PAD results from atherosclerotic occlusive disease in the arteries to the lower extremities, systemic abnormalities affecting whole body O(2) delivery or vascular function in PAD could also partially explain the exercise impairment. To date, the effects of these systemic abnormalities have not been evaluated. To test the hypothesis that the slowed pulmonary Vo(2) kinetics in PAD reflects local and not systemic abnormalities, Vo(2) kinetics were evaluated after the onset of constant-load exercise of the upper and lower limbs in PAD patients and healthy controls (Con). Ten PAD patients and 10 Con without significant cardiopulmonary dysfunction performed multiple transitions from rest to moderate-intensity arm ergometry and treadmill exercise to assess their Vo(2) kinetic responses. Reactive hyperemic (RH) blood flow was assessed in the arms and legs as a measure of endothelial function. Compared with Con, PAD Vo(2) kinetic phase 2 time constants were prolonged during treadmill exercise (PAD 34.3 +/- 9.2 s vs. Con 19.6 +/- 3.5 s; P < 0.01) but not arm exercise (PAD 38.5 +/- 7.5 s vs. Con 32.5 +/- 9.0 s; P > 0.05). RH blood flow was significantly reduced in the legs (PAD 20.7 +/- 8.3 vs. Con 46.1 +/- 17.1 ml.100 ml(-1).min(-1); P < 0.01) and arms of PAD subjects (PAD 34.0 +/- 8.6 vs. Con 50.8 +/- 12.2 ml.100 ml(-1).min(-1); P < 0.01) compared with Con, but RH limb flow was not correlated with arm or treadmill Vo(2) kinetic responses in either group. In summary, slowed pulmonary Vo(2) kinetics in PAD patients occur only with exercise of the lower limbs affected by the arterial occlusive disease process and are not slowed with exercise of the unaffected upper extremities compared with controls. Furthermore, the slowed pulmonary Vo(2) kinetics of the lower extremity could not be explained by any abnormalities in resting cardiac or pulmonary function and were not related to the magnitude of reduction in limb vascular reactivity.