Non-suppression of cortisol by dexamethasone has been described as a biological marker of a diagnostic subgroup of depressed patients. This paper presents the hypothesis that the degree of non-suppression is a variable that reflects the quantity of stress or distress experienced by the patient rather than relating to a specific diagnosis. Such a quantitative measure of stress would be valuable for research in general medicine as well as in psychiatry. Testing of this postulate should apply a more precise interpretation of endocrine principles than has been applied to the dexamethasone suppression test to date.