OBJECTIVE The purpose of the study was to determine whether the dexamethasone suppression test (DST) would discriminate between outpatient adolescents with major depressive disorder and normal adolescent comparison subjects. METHODS Depressed patients were accepted into the study only if they fulfilled the Research Diagnostic Criteria for major depressive disorder. The depressed subjects (N = 44) and the normal subjects (N = 38) were studied in the same environment and under the same conditions. The subjects received 1 mg of dexamethasone at 11:00 p.m. The next day, blood for determining plasma cortisol concentrations was drawn through an indwelling catheter every 60 minutes from 8:00 a.m. until 11 p.m. RESULTS After dexamethasone, the cortisol levels of the adolescents with major depressive disorder and the normal subjects were not significantly different. Only six (14%) of the depressed subjects and one (3%) of the normal subjects showed evidence of nonsuppression (cortisol value greater than 5 micrograms/dl). Analyses of subgroups of the depressed patients based on suicidal tendencies and endogenous subtype also failed to reveal significant differences in cortisol values. Estimates of the severity of depression showed significant negative correlations with cortisol values among the depressed patients. CONCLUSIONS In contrast with previous studies of adolescent inpatients, the DST did not discriminate between the adolescent outpatients with major depressive disorder and the normal comparison subjects in this study. Possible reasons for the discrepancies, such as severity of the depression and inpatient status, are discussed.