Acute administration of cortisol increases non-rapid-eye movement (non-REM) sleep, suppresses rapid-eye movement (REM) sleep and stimulates growth hormone (GH) release in healthy subjects. This study investigates whether cortisol has similar endocrine and electrophysiological effects in patients with depression who typically show a pathological overactivity of the hypothalamus-pituitary-adrenal (HPA) system. Fifteen depressed inpatients underwent the combined dexamethasone/corticotropin-releasing hormone test followed by three consecutive sleep EEG recordings in which the patients received placebo (saline) and hourly injections of cortisol (1mg/KG BW). Cortisol increased duration and intensity of non-REM sleep in particular in male patients and stimulated GH release. The activity of the HPA axis appeared to influence the cortisol-induced effects on non-REM sleep and GH levels. Stimulation of delta sleep was less pronounced in patients with dexamethasone nonsuppression. In contrast, REM sleep parameters were not affected by the treatment. These data demonstrate that the non-REM sleep-promoting effects of acute cortisol injections observed in healthy controls could be replicated in patients with depression. Our results suggest that non-REM and REM sleep abnormalities during the acute state of the disease are differentially linked to the activity of the HPA axis.