In order to test the hypothesis that cortisol secretion is inhibited during sleep, six healthy young men (ages 18-24) were studied in a 4-day protocol. A baseline nocturnal sleep period was followed by one night's total sleep deprivation, then sleep at 180 degrees phase shift, and then return to a normal nocturnal sleep episode (SP-3). Plasma cortisol concentrations were measured every 20 min (obtained by an indwelling venous catheter), rectal temperature was measured every minute, and sleep was polygraphically defined. During the first 4 h of sustained sleep, cortisol secretion was decreased even when sleep occurred during a time when the subject was usually awake; conversely, it was elevated if awake at the usual daily time of sleeping. This was not the case for the last 4 h of sleep. Body temperature was also decreased but during each entire 7- to 8-h sleep period. Meals produced only a small brief rise of cortisol and produced no change in body temperature. Stage 4 sleep was increased during the 180 degrees inverted sleep episode and decreased during SP-3, REM sleep however was increased during SP-3. A reciprocal relationship was found between REM and stages 3 and 4 for the second, third, and fourth, and sixth h of sleep for SP-3. These results demonstrate the inhibitory effect of the behavioral complex of sleeping on cortisol secretion superimposed on its endogenous circadian and ultradian rhythm. These neurophysiological events may be used to entrain and time the period and phase of biological rhythms in relation to shift work, sleep deprivation, and transmeridian jet travel.