Corticotropin-releasing hormone (CRH) plays a key role in coordinating neuroendocrine, metabolic and behavioral responses in stress and affective disorders. To further investigate the effects of enhanced pituitary-adrenocortical activity upon sleep-related phenomena we administered four intravenous injections of 50 µg human (h)-CRH or saline to 11 normal males at 10 p.m., 11 p.m., 12 p.m. and 1 a.m. and measured plasma levels of cortisol and growth hormone (GH) as well as sleep EEG recordings throughout the night. Treatment with h-CRH resulted in a significant increase of mean (± SEM) cortisol secretion between 11 p.m. and 3 a.m. (h-CRH: 100.6 + 9.5 ng/ml; saline: 39.0 ± 1.5 ng/ml; p < 0.01). This initial cortisol increase after repeated h-CRH stimulations was followed by a period of attenuated plasma cortisol between 3 and 7 a.m. (h-CRH: 70.3 + 7.0 ng/ml; saline: 115.5 ± 8.0 ng/ml; p < 0.01). Cortisol surges after h-CRH were associated with a significant blunting of sleep-related GH release expressed as areas under concentration curves (h-CRH: 1.245 ± 0.32 ng/ml/min · 103; saline: 2.462 + 0.92 ng/ml/min· 103, p < O.01). In addition to these hormonal effects, h-CRH induced a decrease of REM and slow wave sleep (stages III and IV) while the amount of more shallow sleep (stages I and II)increased. These effects upon sleep structure were more pronounced during the second part of the night. We conclude that h-CRH induces effects in healthy humans (GH blunting and SWS reduction) which resemble those seen among hypercortisolemic depressives and surmise that CRH plays a role to mediate endocrine as well as behavioral phenomena in the affective dis