Modafinil is an alerting substance which has been used successfully to treat narcolepsy. Nothing is known about its effect on hormone secretions. For this purpose, eight healthy young men were enrolled in a double blind trial to test the effects of modafinil on daily plasma melatonin, cortisol and growth hormone (GH) rhythms. Blood was sampled for hormone assays, every hour during the daytime and every 30 min during the nighttime. In addition, rectal temperature and mental performances were determined during the study which comprised 3 sessions, two weeks apart: a 24 h control session including a night with sleep (S1) and two 48 h sessions S2 and S3 with a sleep-deprived night (N1) followed by a recovery night (N2). Modafinil (300 mg x 2) or placebo were randomly attributed during N1 at 22 h and 8 h. As expected, performance was improved after modafinil administration and body temperature was maintained or increased. Plasma melatonin and cortisol profiles were similar after modafinil and placebo administration. The levels observed during the recovery and the control nights (N2) displayed no difference. For GH, during both sleep deprived nights, secretion was dramatically reduced compared with the control one, although the number of secretory episodes was unchanged. These data show that the alerting property of modafinil is not related to an alteration of hormone profiles and suggest that the acute modafinil administration is devoid of short-term side-effects.