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Recent literature suggests that sleep deprivation has a general stimulatory effect on the central serotonergic system. Herein we report that in hamsters, sleep deprivation induced by gentle handling for 3 h under dim red light at midday stimulates serotonin release in the suprachiasmatic nuclei by as much as 171%. Basal levels of 5-HT release are re-established within 1 h after cessation of treatment. Sleep deprivation also evokes phase advances of the circadian activity rhythm averaging 2 h. When sleep deprivation is undertaken in bright light, serotonin release is stimulated, but phase-shifting is greatly inhibited. It is therefore proposed that if the phase-resetting response to sleep deprivation is mediated by increased serotonin release, light inhibits the phase-resetting effect by blocking the postsynaptic or other downstream actions of serotonin.