It is important to know the effects of prolonged repetitive nerve stimulation (RNS) when it is used in neurophysiological studies. RNS with up to 100 supramaximal stimuli was given to the median, ulnar, and peroneal nerves of normal subjects and the ulnar nerves of subjects with early amyotrophic lateral sclerosis (ALS), recording evoked compound muscle action potentials (CMAPs). In all nerves, there was a decline in the CMAP area and a decrease in CMAP duration. For the peroneal nerve there was a decline in the CMAP amplitude, but a similar decline was not seen in the median or ulnar nerves. Cooling of the muscles resulted in decrement of both the amplitude and area with RNS. In ALS subjects, CMAP amplitude and area both declined after RNS of the ulnar nerve. In this study we describe the changes in CMAP with prolonged RNS among commonly tested normal nerves. Our findings have important implications with regard to RNS.