The urinary excretion rates of norepinephrine were assayed in 26 patients diagnosed as major depressive disorders (primary, unipolar), before and after 14 days of treatment with the monoamine oxidase inhibitor Moclobemide (Ro 11-1163). A standardized 1-h urine collection procedure was used and norepinephrine was assayed by liquid chromatography with electrochemical detection. Norepinephrine was found significantly increased in depressed patients when compared with a control population. The psychotic patients showed the highest excretion rates although they were not significantly different from the endogenous (non-psychotic) group. Urinary norepinephrine output significantly decreased after 14 days of treatment with Moclobemide. This decrease was also marked in those patients that did not show any therapeutic effect. A clear antidepressant effect, shown by a significant decrease of the Hamilton Scale scores for depression, was apparent as early as the 7th day. Increased norepinephrine in melancholic patients was taken as a presumptive indication of altered sympathetic activity.