Desipramine, an active metabolite of imipramine, was administered to 129 patients with severe depressive disorders. The majority had a history of 1 to 4 depressive attacks. In most cases, the drug was given for 2 to 4 months in daily doses of 75 or 100 mg. (i.m.) for a few days, followed by 100 to 150 mg. orally, thereafter. Tranquilizers were given concurrently as required to control agitation, anxiety or insomnia.Desipramine produced a satisfactory clinical response in 99 (76.4%) patients. Compared to imipramine, used in previous studies, the new drug seems to be slightly more potent on a dose-size basis; it has a faster onset of action, evident in 2 to 7 days, and side effects appear to be milder and of shorter duration.Because of its rapid onset of action and mild side effects, desipramine may prove particularly useful in reducing the need for prolonged hospitalization in severe depressive conditions.