Twenty-five unmedicated hospitalized patients, ages 26-64, with severe major depressive disorders, endogenous subtype, were evaluated both clinically and endocrinologically. Although measures reflecting cortisol secretion did not correlate with symptom dimensions and diagnostic subtypes, we did find a significant relationship between cortisol secretion and age during endogenous depressive illness; this included the mean 24 hour plasma cortisol, assessed by sampling every 30 minutes for 24 hours, as well as other single plasma cortisol assessments on other days. After clinical recovery, when plasma cortisol levels returned to normal, there was no significant relationship between cortisol secretion and age. Replication is required of this apparent interaction among age, depressive illness, and cortisol secretion. The result may relate to the proposed role of brain noradrenalin in tonically inhibiting cortisol secretion, the decline of hypothalamic noradrenalin with age, and the hypothesized deficit in depressive illness.