While the physiology of the normal carotid baroreflex is reasonably well established, the pathophysiology of carotid sinus hypersensitivity (CSH) remains obscure. It has been proposed that central α2 adrenoceptor upregulation provides the substrate for the changes in baroreflex gain which manifest as CSH.1 This hypothesis suggests that carotid sinus stiffness resulting from age related cardiovascular disease causes relative diminution of afferent baroreceptor neural traffic, with compensatory brain stem post-synaptic α2 adrenoceptor upregulation. This physiologic denervation hypersensitivity then causes the overshoot bradycardia and hypotension following carotid sinus stimulation that is clinical CSH. Though widely quoted, this hypothesis has no evidence base, and no attempts have been made to date to test it. If α2 adrenoceptor hypersensitivity was the major pathophysiological defect in CSH, a centrally active α2 adrenoceptor antagonist should abolish or attenuate the effects of carotid sinus massage (CSM) in such individuals.1,2 In order to test this hypothesis we studied the effects of the central α2 adrenoceptor antagonist yohimbine3 on the vasodepressor response to CSM in syncopal subjects with CSH, in a randomised, double blind, placebo controlled study, utilising a crossover design.