Plasma cortisol levels were determined every 20 min for 24 hr in depressed adolescents (n = 27) meeting research diagnostic criteria (RDC) for major depressive disorder (MDD) and normal controls (n = 32). All subjects were between 12 and 18 years of age, at least Tanner Stage III of sexual development, medically healthy, and medication free at the time of the studies. The results showed that cortisol secretory patterns were very similar between the two groups with the exception that the depressed adolescents showed significantly elevated cortisol levels around sleep onset (a period when cortisol is usually suppressed). Subgroup analyses showed that most of these differences were contributed by the suicidal/inpatient depressed adolescents. The cause of the elevated cortisol during the normally quiescent period warrants further investigation and may be related to other biological disturbances around sleep onset (difficulty initiating sleep, reduced rapid eye movement (REM) latency, and alterations in sleep-stimulated growth hormone secretion).