The sleep-inducing mechanisms of L-Tryptophan (L-Trp) are generally thought to be mediated by a central serotonergic activation. Evidence is presented that some effects of L-Trp on sleep may be mediated by melatonin, a Trp-metabolite with sedative properties. Trp effects on vigilance, sleep, and plasma-melatonin concentrations were measured after double-blind application of 0, 1, 3, and 5 g L-Trp in nine and five healthy probands during daytime and nighttime, respectively. A significant sleep-inducing effect was observed after L-Trp administration during daytime and nighttime. The infusions of L-Trp caused a massive elevation of plasma melatonin levels. This effect was significant both during the night and the day, indicating that the increment of circulating melatonin may be of extrapineal origin.