Although autonomic failure, parkinsonism, and cerebellar and pyramidal signs are well documented in multiple system atrophy, much less is known about the frequency and severity of involvement of the peripheral nervous system. The frequency and nature of peripheral nerve involvement has therefore been determined in 74 patients with multiple system atrophy using nerve conduction studies and skeletal muscle EMG. These findings were compared with those on sphincter EMG. Ninety per cent of the patients had an abnormal sphincter EMG, indicating denervation and reinnervation consistent with anterior horn cell loss in Onuf's nucleus, but only 40% had either abnormal nerve conduction studies (mixed sensorimotor axonal neuropathy in 17.5%) or abnormal skeletal muscle EMG (suggesting partial denervation in 22.5%). These data indicate a remarkable selective vulnerability of the anterior horn cells of Onuf's nucleus innervating external sphincter muscles relative to those supplying skeletal muscle in patients with multiple system atrophy. If this selective pattern of involvement can be explained it may be a clue to pathogenetic mechanisms in multiple system atrophy.