Identifying severe stress is an important basis for treating and preventing many diseases. The quantification of biological stress markers presents a safe and efficient possibility to evaluate the effects of stressors, independently of their underlying cause.

Cortisol is the most important stress hormone besides catecholamines. The formation of cortisol in the adrenal cortex is stimulated by the adrenocorticotropic hormone (ACTH) from the anterior lobe of the pituitary gland, whose release is stimulated by the corticotropin-releasing hormone of the hypothalamus. Cortisol inhibits the release of ACTH in the pituitary gland by means of a negative feedback mechanism. This complex series of regulatory influences is called hypothalamic-pituitary-adrenal axis (HHNA) or stress axis.

The synthesis and release of cortisol takes place in a circadian rhythm. It is highest one hour after the mean individual morning wake-up time and lowest during the first hours of nightly sleep. Cortisol in blood is mainly bound to proteins. Only free cortisol is biologically active and small enough to diffuse unhindered into the saliva. Saliva is therefore excellently suited for determination of the biologically active hormone.