The efficacy and safety of fluoxetine, a new antidepressant agent, were assessed in a double-blind, parallel, randomized study of 44 outpatients with major depressive disorder. Following a 1-week placebo period, patients were randomly assigned to either fluoxetine or amitriptyline for a period of 5 weeks. The mean maintenance dosages were 55 mg/day for fluoxetine and 159 mg/day for amitriptyline. Both drugs were effective in relieving the symptoms of depression. The most frequently reported side effects were nausea and nervousness for fluoxetine, and dry mouth, dizziness, and drowsiness for amitriptyline.