Respiratory insufficiency is a major cause of death in Duchenne muscular dystrophy (DMD). The earliest sign is a hypoventilation which appears in REM sleep. We administered 20 mg of clomipramine hydrochloride before sleep to two DMD patients with periodic nocturnal hypoxemia. The complaints such as morning headache, nausea and somnolence disappeared promptly. Polysomnography revealed complete suppression of REM sleep and disappearance of periodic hypoxemia in both cases. The most important untoward effect was intractable constipation observed in one patient. Although clomipramine dramatically improved the nocturnal periodic hypoventilation, the therapeutic effects lasted less than three months. Permanent REM sleep suppression is requisite for optimal drug therapy of periodic nocturnal hypoventilation in DMD.