The aim of the present study was to assess the usefulness of the selective serotonin-reuptake-inhibitor S-Citalopram as a serotonergic challenge probe in 24 healthy male and 24 healthy female participants. The participants received a single oral dose of 10 and 20mg of S-Citalopram in a placebo-controlled double blind crossover design. In female subjects phases of the menstrual cycle were controlled. Changes in concentrations of cortisol in saliva were used to indicate serotonergic reactivity. S-Citalopram induced a reliable dose dependent rise in cortisol concentrations. Results reveal a clear dose-response relationship in both sexes. However, in contrast to the 10mg condition the dosage of 20mg led to significantly higher cortisol levels in females, whereas no differences could be observed with respect to different phases of the menstrual cycle (follicular vs. luteal). Adverse side effects were reported only after 20mg. The results clearly indicate that the dosage of 10mg should be preferred when challenging males and females. Results will be discussed with regard to the further use of S-Citalopram in neuroendocrine challenge tests.