The Hamilton Depression Rating Scale (HDRS) score and plasma cortisol values were measured in 100 depressed patients at 8 a.m., 4 p.m. and 11 p.m. after oral administration of 1 mg dexamethasone the previous night. The patients were categorized according to DSM-III as suffering from either minor depression (including dysthymic disorder, 300.40; adjustment disorder with depressed mood, 309.00; atypical depression, 296.82) or major depression (without melancholia, 296.X2; with melancholia, 296.X3; with psychotic features, 296.X4). Plasma cortisol levels of greater than or equal to 3.5 micrograms/dl at 8 a.m. were found to be the most sensitive (56.9%) and specific (94.3%) discriminator between minor and major depression. Plasma cortisol levels at 4 p.m. and 11 p.m. or the combination of several cortisol values also differentiated between minor and major depression; however, the results were not so conclusive. According to the ratings on the Hamilton Depression Scale the patients with major depression were more severely depressed (P less than 0.001) than patients suffering from minor depression. Cortisol values at 8 a.m., 4 p.m., 11 p.m. and the highest levels were significantly (P less than 0.001) correlated with the HDRS score. A maximum of 20.2% of the score variance could be explained by the correlation with the highest cortisol value observed. Severity of illness does not exclusively account for the biological differences between minor and major depression.