Changes in intracortical inhibition have been detected by means of paired-pulse transcranial magnetic stimulation (TMS) based on electromyographic recordings in many neurological or psychiatric disorders, including amyotrophic lateral sclerosis (ALS). By contrast, inhibitory responses have been generally overlooked in single motor unit (MU) studies in patients with ALS. The aim of this study was to investigate the TMS-induced inhibitory responses of single MUs in peristimulus time histograms and the changes observed with time. For this purpose, 263 MUs were tested in 10 ALS patients in two to four recording sessions. Upon subdividing the data into epochs corresponding to mean disease durations of 12, 20, 32, 43, and 168 months, we found that inhibitory responses occurred more frequently than normal throughout the course of the disease and were stronger than normal during the first year after disease onset. This finding argues against the hypothesis that loss of inhibition may be part of the pathogenic process in ALS.