The mixed nerve silent period (MNSP) is the period of motor inhibition observed when the mixed nerve innervating a voluntary activated muscle is electrically stimulated. The etiology of the MNSP is multifactorial, with the early and middle phases likely to be related to the effects of antidromic motor nerve activity on peripheral nerve and spinal interneurons. The terminal portion of the MNSP is mediated primarily by small diameter myelinated afferent fibers. The duration and latency of the MNSP vary as a function of both strength of stimulation and level of voluntary activation. In this study, we varied both stimulus strength and exertion, and compared MNSPs in 6 normal subjects with those obtained from 8 patients with amyotrophic lateral sclerosis (ALS). Differences between patients and control subjects included a longer duration of the MNSP in ALS patients, as well as less complete inhibition in the middle phases of the period. The longer duration of the MNSP may reflect an abnormality of sensory motor processing in ALS patients. The physiology underlying the incomplete inhibition is unclear, but may reflect abnormalities in Renshaw cell function.