The defect of neuromuscular transmission is one of the important signs in ALS. The amplitude of a single motor unit potential from patients with ALS often decrease during tonic voluntary contraction. This phenomenon is closely correlated with fatigue seen in the patient. Overfunctioning of Ach release in the nerve terminal might cause the failure of neuromuscular transmission in ALS. Fasciculations is an another characteristic sign and considered mainly to be peripheral axons in origin. It is postulated that the dysfunction of potassium channel in ALS axons makes the hyperexcitability of the axon membrane, causing fasciculations. Magnetic cortical stimulation sometimes evokes the same potentials as fasciculations, implying the hyperexcitability might be present also in spinal motoneurons or even in pyramidal neurons in ALS. All of these findings lead to the hypothesis that hyperexcitability or overactivity of central and peripheral motoneurons is an essential feature in ALS.