Six patients with amyotrophic lateral sclerosis were given from 800 to 4000 micrograms of thyrotropin-releasing hormone (TRH) intrathecally for a period of 2-6 months. The progressive course of this disease, manifested by increasing atrophy, paralysis and disability score, was not altered. This supports the hypothesis that the decrease in TRH content in the anterior horn region is secondary to the cellular destruction. TRH appears to play no significant role in the pathogenesis of amyotrophic lateral sclerosis.