Résumé : The temporal profiles of subjective fatigue (as assessed by the Stanford Sleepiness Scale), of cognitive performance (on a digit symbol substitution test and a symbol copying task), of body temperature, and of the peripheral concentrations of melatonin, thyroid-stimulating hormone (TSH), and cortisol were obtained simultaneously at frequent intervals in 17 normal young subjects submitted to a 43-h period of constant routine conditions involving continuous wakefulness at bed rest in dim indoor light. The subjects had knowledge of time of day. Caloric intake was exclusively in the form of an intravenous glucose infusion, and plasma glucose levels were monitored continuously in 8 of the 17 subjects. Under these conditions, fluctuations in plasma glucose reflect primarily changes in glucose use because endogenous glucose production is suppressed by the exogenous infusion. Following the completion of a baseline constant routine study, the volunteers participated in two subsequent studies using the same protocol to determine the immediate psychophysiological effects of exposure to a 3-h pulse of bright light or to a 3-h pulse of physical exercise. Sleepiness and performance varied in a mirror image, with significant negative correlations. Sleepiness scores were minimal around noon and then increased at a modest rate throughout the rest of the normal waking period. Staying awake during usual bedtime hours was associated with an acceleration in the rate of increase in sleepiness, which coincided with decreasing body temperature, rapidly rising cortisol concentrations, and maximal levels of melatonin and TSH. When body temperature reached its nadir, a further major increase in sleepiness occurred in parallel with a pronounced decrease in plasma glucose (reflecting increased glucose use). Recovery from maximal sleepiness started when blood glucose levels stopped falling and when significant decreases in cortisol and melatonin concentrations were initiated. Lower levels of subjective sleepiness resumed when glucose concentrations and body temperature had returned to levels similar to those observed prior to sleep deprivation and when melatonin and TSH concentrations had returned to daytime levels. The synchrony of behavioral, neuroendocrine, and metabolic changes suggests that circulating hormonal levels could exert modulatory influences on sleepiness and that metabolic alterations may underlie the sudden increase in fatigue consistently occurring at the end of a night of sleep deprivation. Effects of bright light or exercise exposure on subjective sleepiness appeared to be critically dependent on the timing of exposure.