An earlier study has shown that angiotensin and catecholamines were responsible for the vasoconstriction observed in the isolated hindlimb preparation during aortic cross-clamping. That study also demonstrated that when vasoconstriction was blocked with an α-adrenergic antagonist, phenoxybenzamine, vasodilation was elicited by aortic cross-clamping. The present study tested the hypothesis that this vasodilation was mediated via β-adrenergic receptors. Eighteen dogs had their hindlimb denervated, vascularly isolated, and pump perfused with blood drained from the inferior vena cava, after passing through a gas-exchanging membrane where oxygen and carbon dioxide tensions were normalized. Left and right thoracotomies were performed, and the aorta and inferior vena cava were cross-clamped. The cross-clamping was associated with 29-37% increase in limb vascular resistance in control dogs (n = 6), in animals pretreated with propranolol (2 mg/kg, n = 6), and in dogs pretreated with a combination of phenoxybenzamine (3 mg/kg) and propranolol (2 mg/kg, n = 6). In animals pretreated with a combination of phenoxybenzamine, propranolol, and enalaprilat (2 mg/kg, n = 6), an angiotensin-converting enzyme inhibitor, limb vascular resistance did not change. This study has confirmed that aortic cross-clamping is associated with vasoconstriction induced by angiotensin and activation of α- adrenoceptors and has further demonstrated that vasodilation is attributable to β-adrenoceptor activation.