1. The efficacy of fluvoxamine is compared to that of desipramine in a multicenter double blind placebo controlled six-week flexible dose trial of 90 outpatients with major depressive disorder. 2. Although overall drug effects were relatively weak, there were trends suggesting separation of both active drugs from placebo at week six. Both drugs were well tolerated. 3. Studies of major depression ought to be designed to last 8-10 weeks in order to demonstrate placebo active drug differences and the stability of such a difference should it occur in the first six weeks.