Twenty-four-hour profiles of pituitary-adrenocortical secretory activity in humans are characterized by a distinct decrease in hormone secretion after sleep onset and a strong increase during the early morning hours. It is a widely accepted notion that this pattern of hormone secretion is driven by intrinsic circadian oscillators, and the contributions of sleep and wakefulness have been greatly neglected. Here, we examined whether there is a sleep-dependent inhibition of stimulated ACTH and cortisol release during early nocturnal sleep, which is dominated by slow wave sleep (SWS). We administered human CRH (hCRH; 50 micrograms), the main corticotropin secretagogue, to 14 healthy men during the first SWS period after sleep onset and another time in the same night during a period of stage 2 sleep in the second half of sleeping time. To discriminate possible circadian influences from influences of sleep, on a second night another two injections of hCRH were administered at identical points during the night to the same subject, who was kept awake. Exclusively during sleep, but only during SWS in the beginning of sleep time, ACTH and cortisol responses to hCRH were blunted. The results demonstrate an inhibiting influence of sleep on stimulated ACTH and cortisol secretion, with this effect restricted to the early part of sleep.