The sympathetic skin response (SSR) was evaluated in 25 patients with amyotrophic lateral sclerosis (ALS) to assess for involvement of the autonomic nervous system. Twenty-two age-matched normals and 6 patients with muscular dystrophy served as controls. The SSR was intact in all normal volunteers and all patients with muscular dystrophy. The mean SSR latency in the ALS patients was prolonged compared to that of normals (2.29 +/- 0.28 versus 2.13 +/- 0.16 s, P < 0.05). The SSR was absent in one or both legs of 10 ALS patients (40%). Absence or abnormal latency of SSR in patients with ALS without clinical findings of autonomic failure suggests involvement of the autonomic nervous system in addition to the motor system.