The relationship between the temporal organization of cortisol secretion and sleep structure is controversial. To determine whether the cortisol profile is modified by 4 hours of sleep deprivation, which shifts slow-wave sleep (SWS) episodes, 12 normal men were studied during a reference night, a sleep deprivation night and a recovery night. Plasma cortisol was measured in 10-minute blood samples. Analysis of the nocturnal cortisol profiles and the concomitant patterns of sleep stage distribution indicates that the cortisol profile is not influenced by sleep deprivation. Neither the starting time of the cortisol increase nor the mean number and amplitude of pulses was significantly different between the three nights. SWS episodes were significantly associated with declining plasma cortisol levels (p less than 0.01). This was especially revealed after sleep deprivation, as SWS episodes were particularly present during the second half of the night, a period of enhanced cortisol secretion. In 73% of cases, rapid eye movement sleep phases started when cortisol was reflecting diminished adrenocortical activity. Cortisol increases were not concomitant with a specific sleep stage but generally accompanied prolonged waking periods. These findings tend to imply that cortisol-releasing mechanisms may be involved in the regulation of sleep.