Noradrenergic fibers from the locus ceruleus were identified in close proximity to brain microvessels, and adrenoceptors exist in isolated brain capillaries. Yet, proof of innervation of brain microvessels by locus ceruleus remains elusive. We now demonstrate increased density of beta-adrenoceptors by pindolol binding in microvessels isolated from the norepinephrine-depleted cerebrum two weeks after locus ceruleus lesion or reserpine treatment. This finding of 'denervation supersensitivity' in brain microvessels implies that their adrenoceptors respond to norepinephrine from the locus ceruleus, and strongly suggests that the locus ceruleus innervates brain microvessels. These results may have important implications because blood-brain barrier dysfunction may be a factor in the pathophysiology of Alzheimer dementia and Parkinson disease, which are associated with locus ceruleus degeneration.