A distinct rise in cortisol levels that occurs after morning awakening is increasingly used as an indicator of adrenocortical activity which is associated with different pathologies. Although it was previously assumed that the transition from sleep to wake is essential for the occurrence of the cortisol morning rise, this has never been tested. Here, we examined 16 healthy young men (20-33 yrs) between 2300 and 0800 h under sleep laboratory conditions. Serum cortisol and plasma adrenocorticotropin (ACTH) as well as salivary cortisol levels (after subjects were woken up at 0700 h) were repeatedly assessed. In a supplementary study condition, salivary cortisol levels in the first hour after awakening were measured at the subjects' home on two consecutive days. Comparison of pre- and post awakening measurements revealed significantly steeper increases in cortisol and ACTH after awakening. The rise in cortisol upon awakening under laboratory conditions did not significantly differ from that observed at home. We conclude that the cortisol increase after awakening is a response to morning awakening that is distinct from the circadian rise in hypothalamo-pituitary-adrenal (HPA) activity in the morning hours. Although the cortisol awakening response is modulated by circadian influences, it primarily reflects phasic psychophysiological processes specific to the sleep-wake transition.