Daytime oral melatonin typically exerts soporific and thermoregulatory effects; however, it is not clear whether these effects reflect the normal physiological response to endogenous nocturnal melatonin production. We infused melatonin at doses that produced physiological and supraphysiological steady-state levels in 24 young adults during two daytime bed rest protocols. From 1000 to 1630, subjects were infused intravenously with saline or melatonin in counterbalanced order. Each group of eight subjects received melatonin (and saline) infusions at one dose rate: 0.04 μg ⋅ h−1 ⋅ kg body wt−1 (low), 0.08 μg ⋅ h−1 ⋅ kg−1(medium), or 8.0 μg ⋅ h−1 ⋅ kg−1(high). Low and medium melatonin infusions produced plasma and saliva levels within the normal nocturnal range observed in young adults. These levels were not associated with any changes in rectal, hand, forehead, or tympanic temperatures or with subjective sleepiness. High melatonin produced supraphysiological plasma and saliva levels and was associated with a significant attenuation in the daytime increase in rectal temperature, significantly increased hand temperature, and greater sleepiness. It is not yet clear whether the thermoregulatory and soporific effects of daytime supraphysiological melatonin administration are equivalent to the physiological responses to endogenous melatonin.