The purpose of this study was to assess the effect of atherosclerosis on the regulation of limb blood flow. To examine this issue, the reactivity of resistance and conduit vessels was evaluated in 11 patients with peripheral atherosclerotic disease and six control subjects. Responsiveness of resistance vessels was measured by venous occlusion plethysmography. Responsiveness of conduit vessels was determined by quantitative angiography to measure the diameter of the superficial femoral artery. To distinguish endothelium-dependent vasodilation from that caused by direct smooth muscle relaxation, each participant received intra-arterial infusions of methacholine and nitroprusside, respectively. Flow-mediated dilation of the superficial femoral artery was determined during reactive hyperemia. Vasoconstrictor function was determined by the infusion of phenylephrine. Methacholine reduced calf vascular resistance in the control subjects but not in the patients with atherosclerosis (-64 +/- 11% versus 6 +/- 18%, p less than 0.01). Nitroprusside decreased calf vascular resistance comparably in each group (-51 +/- 5% versus -42 +/- 4%, p = NS). The vasoconstrictor effect of phenylephrine was similar in each group (105 +/- 30% versus 108 +/- 22%, p = NS). In the superficial femoral artery, the vasodilator responses to both methacholine (20 +/- 4% versus 1 +/- 4%, p less than 0.05) and nitroprusside (19 +/- 4% versus 5 +/- 4%, p less than 0.05) were blunted in the atherosclerotic patients as was the vasoconstrictive response to phenylephrine (-15 +/- 1% versus -1 +/- 5%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)