Despite the rarity of such observations in autopsy material, peripheral nervous system involvement in patients with multiple sclerosis is more common than suspected, judging from results of sophisticated electrophysiological and teased nerve fiber studies. The existence of a number of well documented cases of overt peripheral neuropathy in MS patients suggests that an etiological link may exist between the two conditions. The proposal has been made that one of the obligatory steps in the pathogenesis of MS is an alteration of the blood-brain barrier, which results in most instances from an immunologically induced vasculopathy due to a non-specific viral infection. Whereas the CNS responds by the formation of MS plaques, the PNS lesion is that of the typical post-infectious inflammatory polyneuropathy. In some MS patients an unusual degree of immunological vulnerability causes onion-bulb formations to develop as a result of repeated antigenic challenges. In MS patients the onion-bulb formation is the PNS analog of the CNS plaque: both result from the same pathogenetic mechanism.