The aim of this work was to investigate the potential chronobiotic properties of slow-release caffeine, in comparison with melatonin, on resynchronization of endogenous melatonin and cortisol secretions after an eastbound flight by jet incurring a time loss of 7 h. A group of 27 reservists of the US Air Force received either slow-release caffeine (300 mg), melatonin (5 mg) or placebo before, during and/or after the transmeridian flight. Saliva and urine were sampled before the flight in the United States (from day -2 to day 0) and after the flight in France (from day 1 to day 10). Saliva was collected once a day on waking to determine saliva melatonin and cortisol concentrations. In addition, concentrations of caffeine in saliva were determined three times a day and of 6-sulphatoxymelatonin in urine collected overnight to check that the treatment regimes had been complied with. From day 3 to day 5, post-flight saliva melatonin concentrations were significantly different from control values in the placebo group only. During treatment with melatonin, the mean urinary 6-sulphatoxymelatonin concentration in the melatonin group was more than twice as high as in the two other groups. In the slow-release caffeine group and the melatonin group, mean saliva cortisol concentrations were significantly lower than control from day 2 to day 5, whereas the placebo group had a mean saliva cortisol concentration significantly lower than the control value from day 2 to day 9. In conclusion, these results indicate that administration of slow-release caffeine, as well as of melatonin, allows a faster resynchronization of hormone rhythms during the 4 days following an eastbound flight incurring the loss of 7 h.