We report 4 cases of amyotrophic lateral sclerosis (ALS) in the totally locked-in state (TLS); 2 of the cases were autopsied. The clinical and pathological findings of ALS reported previously were essentially included in those studied here. In all cases reported in this paper, the voluntary muscles, including the oculomotor muscles, deteriorated rapidly, resulting in respiratory failure within 1.5 years. Successive observation of the 4 cases confirmed that ontogenetically old motor functions, including oculomotor functions, were preserved in the advanced stage, and that the main lesions in the oculomotor system were supranuclear. The 2 autopsied cases showed widespread pathological lesions other than those of the pyramidal tract and motoneurons commonly seen in ALS. We review these findings, and discuss them from an ontogenetical aspect in terms of the development of motor functions and anatomical myelination, and compare them with clinico-pathological findings of progressive supranuclear palsy (PSP) and anatomical structures of the supranuclear oculomotor system in monkeys.