Spontaneous plasma cortisol was measured in the interval from 15.00-18.00 h 74 hospitalized depressed patients (56 endogenously and 18 non-endogenously depressed according to the Newcastle index). The cortisol value at the individual time points correlated well with the mean cortisol concentration with the best correlation in the interval between 16.00 and 17.00 h (RHO = 0.89-0.92). For most patients maximum cortisol concentration was found early in the sampling period. Plasma cortisol was high during depression and was reduced after recovery in both diagnostic groups. Correlation between plasma cortisol during depression and type of depression or degree of depression was poor indicating that spontaneous plasma cortisol might have only a limited diagnostic value. However, among the endogenously depressed patients those not responding to treatment with cyclic antidepressants alone had significantly higher cortisol levels prior to treatment than responders. Afternoon plasma cortisol thus may be used as a predictor of the outcome of treatment with cyclic antidepressants.