The purpose of this study was to determine if intraarterial vasodilating drugs could augment the vasodilation produced by sympathetic blockade, such as occurs during epidural anesthesia. Papaverine (2 mg/min), nitroglycerin (1 microgram/kg/min), aand saline were infused into the femoral artery before and after lumbar sympathectomy in six arterially isolated canine hindlimbs. Femoral blood flow was controlled with a perfusion circuit at baseline (80 ml/min), half-baseline (40 ml/min), and low (5 ml/min) flow rates so that hindlimb mean arterial pressure served as an index of peripheral vasodilation. At low flow, hindlimb arteriovenous oxygen content difference increased from 1.4 (baseline) to 6.2 ml O2/dl, consistent with peripheral ischemia. At baseline flow before sympathectomy, papaverine and nitroglycerin caused a decrease in hindlimb mean arterial pressure of 30% and 18%, respectively (p less than 0.01 vs saline control), equivalent to the decreases of 31% and 16% after sympathectomy (p less than 0.01). At half-baseline, papaverine and nitroglycerin reduced hindlimb mean arterial pressure by 22% and 12%, respectively (p less than 0.01), and caused comparable vasodilation after sympathectomy. Neither drug significantly changed hindlimb mean arterial pressure at low flow. Sympathectomy itself reduced hindlimb mean arterial pressure by 23% at baseline flow (p less than 0.01), by 18% at half-baseline flow (p less than 0.01), but had no effect at low flow. We conclude that intraarterial papaverine and nitroglycerin cause peripheral vasodilation that is synergistic with sympathectomy-induced adrenergic blockade, but they cannot augment vasodilation caused by peripheral ischemia.