The effectiveness of codeine as a treatment for the excessive daytime sleepiness of narcolepsy was studied in two experimental trials. In an open trial of codeine in five narcoleptic subjects, dramatic clinical improvement was reported. However, all-night polysomnography and maintenance of wakefulness tests before and after codeine showed no significant differences. A double-blind placebo-codeine trial was conducted in which eight narcoleptic subjects received codeine for 1 week and placebo for 1 week in a random order. During the week they kept a diary, and on the sixth evening and for 10 h following awakening on the seventh day they were monitored by radiotelemetry in the sleep laboratory for electroencephalogram, electro-oculogram, and electromyogram. The results were analyzed for sleep stages as well as four levels of wakefulness. The results showed no significant differences in any of the objective sleep or wakefulness parameters. However, the diaries showed significantly fewer naps during the week on codeine as compared with the placebo week. Eighteen of 27 narcoleptic patients treated with codeine report clinical improvement. Codeine consistently results in subjective clinical improvement. However, this is not reflected in the objective measures generally used to assess daytime sleepiness.