We tried melatonin treatment in two patients with non-24 h sleep-wake syndrome, who did not respond to treatments by vitamin B12, bright light therapy, or hypnotics. In one patient, melatonin 5-10 mg improved difficulty in falling asleep and in waking, although it failed to improve the sleep-wake rhythm. In another patient, melatonin 3 mg successfully changed the sleep-wake rhythm from free-running pattern to delayed sleep phase pattern. However, melatonin re-administration after a 4-month drug-free interval failed to improve his free-running sleep-wake rhythm. These results suggest that melatonin acted as a sleep inducer in one patient and as a phase setter in the other, although the effect on the latter patient was transient.