The results of clinical and polysomnographical examinations on 11 Japanese Rett syndrome cases were summarized to substantiate further our previous results regarding the pathophysiology of the disease. It was concluded that the disease starts early in infancy and takes a progressive course. Each characteristic symptom appears in an orderly sequence which is thought to reflect the sequential systemic involvement of certain neuronal systems. Based on the characteristic symptoms and signs, and polysomnographical studies, we speculated that the initial lesion was the locus coeruleus with a hypoactive noradrenergic system combined with other hypoactive monoaminergic systems, including those of serotonin and dopamine, occurring along with the early developmental course. In later stages, hyperfunction possibly due to postsynaptic supersensitivity of the dopamine system causes the characteristic symptoms of the Rett syndrome.