Recent research provides evidence for an interaction between sleep and the activation of the hypothalamic-pituitary-adrenal (HPA)-axis, but detailed studies in patients are still missing. We investigated hourly evening and nocturnal plasma cortisol secretion and sleep in seven male patients with severe chronic primary insomnia and age- and gender-matched controls. Evening and nocturnal cortisol levels were significantly increased in patients. Evening cortisol correlated with the number of nocturnal awakenings in patients and controls. Additionally, patients showed significant correlations between sleep parameters and the first 4 h of nocturnal cortisol secretion. These results are indicative of changes in the HPA system in insomnia and may reflect a pathophysiological mechanism of chronic insomnia resulting in a vicious cycle of both disturbed HPA functions and chronic insomnia according to the arousal hypothesis of insomnia.