In depressed patients neuroendocrine challenge tests have revealed a blunted reaction to serotonergic stimuli in terms of a significantly reduced hormonal response of prolactin and cortisol secretion. As a selective serotonergic neuroendocrine challenge the Citalopram Challenge Test has already proved to possess a strong effect on cortisol and prolactin secretion in healthy volunteers. In the present study 20 controls and 20 patients suffering from an acute episode of major depression underwent neuroendocrinological stimulation with 20 mg citalopram and with placebo.In the group of the depressed patients prolactin and cortisol secretion was compared with the stimulation procedure with 20 mg citalopram and placebo stimulation. For both hormones no differences were found between the two conditions, neither for the area under the curve (AUC) as measurement of total hormone secretion nor for the peak of hormone secretion. Significant differences of hormone secretion were shown between depressed patients and controls (AUC of prolactin: 598.1 ng/ml 90 min vs. 118.1 ng/ml 90 min; p < 0.05). These results support the hypothesis of serotonergic hypofunction in depressed patients.