The neuronal mechanisms of sleep generation, in particular synchronization of brain activity in the process of non-rapid-eye movement (non-REM) sleep, has been elucidated in the past decade. A previous study of our group showed that acute administration of cortisol is known to increase slow-wave sleep and suppress rapid-eye movement (REM) sleep in man. To further elucidate the non-REM sleep-promoting effects of cortisol with respect to the synchronization of cortical activity, it is important to establish a sleep-state-specific quantitative EEG analysis. We therefore investigated the effects of repetitive injections of hydrocortisone on spectral composition of sleep EEG in 10 healthy male young volunteers. In addition, we performed high-frequency blood samplings to assess the relation between changes in the sleep EEG and sleep-associated secretion of growth hormone (GH). Cortisol administration resulted in a significant increase in highly synchronized EEG activity including delta and theta frequencies, according to a higher amount of slow-wave sleep. This effect predominated in the first few hours of night sleep. REM sleep was decreased, which appeared to be secondary to the lengthened first sleep cycle. The cortisol-induced stimulation of GH release did not occur in correspondence with the increased slow-wave activity. In view of the sleep impairing properties of corticotropin-releasing hormone (CRH) and the sleep-promoting function of GH-releasing hormone, it appears likely that a negative feedback inhibition of endogenous CRH was the key mechanism mediating the observed results. The cortisol-induced effects on sleep intensity and sleep-associated GH secretion appeared to be driven by different mechanisms.