This study was performed to determine to what extent the morphology of the rabbit middle cerebral artery is affected by the absence of the sympathetic nervous system. Six weeks after unilateral ablation of the superior cervical ganglion, which induced ipsilateral degeneration and disappearance of the perivascular noradrenergic nerve fibers, comparison between the ipsi- and the contralateral middle cerebral arteries revealed that the denervated arterial wall underwent significant thickening. This thickening was principally due to hypertrophy of the smooth muscle cells (SMC), together with an increase in the amount of medial and adventitial collagen. The hypertrophied SMC showed important morphological and ultrastructural modifications – irregular shape, increase in the number of organdies (particularly of Golgi apparatus, free ribosomes, rough endoplasmic reticulum and microtubules), large indented nuclei rich in euchromatin – indicating profound changes in their metabolic and contractile activity which could result in an alteration of their mechanical properties. As these alterations were strictly ipsilateral to the sympathectomy it is likely that they are the direct consequence of the suppression of a regulatory ‘trophic’ factor linked to the presence of sympathetic nerve fibers. This concept is reinforced by the fact that the first SMC affected are those situated at the media/adventitial border, in the vicinity of adventitial nerve bundles. Thus, the sympathetic nervous system appears to play a key role in the long-term regulation of the cerebral vascular tree structure.