• Depressed patients commonly have disturbances in their sleep and cortisol secretory patterns. When the sleep-related changes in plasma cortisol concentration were measured in 14 patients with a primary major depressive illness, they differed significantly from the changes measured in 14 age- and sexmatched healthy control subjects. The nadir of the nocturnal plasma cortisol concentration was significantly greater in the group of depressed patients, and the nocturnal increase in the plasma cortisol concentration occurred significantly closer to sleep onset in these patients. The circadian activity within the hypothalamic-pituitary-adrenal axis of these depressed patients showed a subtle but significantly disturbed temporal relationship to sleep onset. This reduced time between sleep onset and the nocturnal increase in cortisol secretion suggests a possible biologic correlate of a depressive illness that might be useful as an illness marker in depressed patients.