SummaryWe studied the effects of modafinil, a putative central α-1 agonist, on the excessive daytime sleepiness (EDS) of 10 narcoleptic patients while using a double-blind design and objective measurements of vigilance. There were two treatment periods, in which either modafinil or placebo was used; each lasted four weeks and was preceded by a 2-week “run-in” period and separated by a 2-week “wash-out” period. The effects of treatment on EDS were evaluated by daily home questionnaires and a psychomotor performance test, the Four Choice Reaction Time Test (FCRTT). Modafinil reduced the daily number of sleep attacks significantly, and markedly improved performances during the FCRTT. Results of this study suggest that modafinil is effective in treating EDS in narcolepsy, and that noradrenergic mechanisms could be involved in the physiopathology of EDS in that disorder.