The secretory activity of the pituitary-adrenocortical axis at night is characterized by a quiescent period during the first hours of sleep, preceding a period of enhanced activity in the early morning hours. It is still controversial whether the typical nocturnal secretory pattern of adrenocorticotropic hormone (ACTH) and cortisol is a mere reflection of a circadian rhythm or whether mechanisms associated with the state of sleep influence the nocturnal secretion of these hormones. Here, we administered arginine vasopressin (AVP) to normal men during the first part of nocturnal sleep and compared the release of ACTH and cortisol with the release after a second administration during the second part of the same night and also with the release after administration of AVP at identical points of nighttime while subjects were kept awake in another night. Compared with wakefulness, the cortisol release in response to AVP was significantly lower during sleep, with this effect restricted to the early part of sleep. The ACTH release was lower after the first AVP administration during the early part of sleep as compared with the AVP injection during the second part of the same night. Our data demonstrate a sleep-associated inhibition of stimulated ACTH and cortisol release, suggesting a period of decreased responsiveness of the pituitary-adrenocortical axis during early sleep.