The rates of onset and offset of α-adrenoreceptor blockade by phentolamine (5 × 10-7 M) have been studied on the normal and denervated rabbit aorta and rat vas deferens. Removal of the adventitia with its accompanying sympathetic nerve component results in an approximately threefold increase in the rate of onset of α-adrenoreceptor blockade by phentolamine in the rabbit aorta. The rate of offset of blockade by the antagonist on the aorta is likewise faster after the adventitia has been removed (approximately threefold faster for loss of 90% of the antagonist from the region of the receptors). This effect is not likely to be attributed to the absence of sympathetic nerve terminals since surgical denervation of the rat vas deferens has no effect on the kinetics of receptor blockade in this densely innervated organ. These data suggest that the adventitia of the rabbit aorta may serve as a diffusion barrier which limits the antagonist’s access to, and efflux from, the region of the receptors. The dissociation constant of phentolamine (calculated from the equilibrium dose ratio) on the α-adrenoreceptor is unaltered by denervation in either tissue and is identical in both tissues. It is suggested that α-adrenoreceptors in the rabbit aorta and rat vas deferens are of a single type and are not significantly affected, with respect to antagonist affinity, by dener