We calculated the percent change in initial vascular resistance during open loop intra-arterial infusions of norepinephrine (NE) in 12 acutely denervated isolated canine brains and 5 acutely denervated perfused hindlimbs. The studies were repeated on seven chronically denervated brains devoid of perivascular sympathetic fibers. All tissues were free of residual anesthetic. Half-maximal responses were obtained at similar plasma NE concentrations in both the control brains (ED50 13.1 +/- 3.8 X 10(-6) M) and hindlimbs (ED50 9.22 +/- 2.3 X 10(-6). The maximal response was much greater in the limb vasculature (490.3 +/- 30.1%) than in the cerebral vasculature (107.2 +/- 9.5%). A fourfold increase in cerebral vascular sensitivity was noted 3 days after sympathetic gangliectomy (ED50 3.44 +/- 0.74 X 10(-6) M), without any significant change in the maximal response (101.3 +/- 5.7%). Plasma levels of NE observed in resting dogs did not constrict either vascular bed; elevated levels of NE observed in stress dogs would minimally constrict limb vessels but not acute or chronically denervated cerebral vessels. These in situ results confirm that NE does not play a significant role as a physiological vasomotor hormone and suggest that prejunctional neuronal uptake of NE is not responsible for the observed differences in cerebral and hindlimb vascular response. Furthermore, it is unlikely that denervation hypersensitivity to circulating NE plays a role in pathological cerebral vasoconstriction (vasospasm) following subarachnoid hemorrhage.