The antidepressant efficacy and side effect profile of a fixed dose of 20 mg/day of fluoxetine, a specific serotonin reuptake inhibitor, were compared to those of amitriptyline. Fifty-eight patients with DSM-III-R depression were randomly assigned to receive either fluoxetine or amitriptyline. Fifty-six patients (fluoxetine N = 23, amitriptyline N = 23) completed the 6 week study. Comparable antidepressant efficacy was demonstrated for the two drugs. Patients taking fluoxetine reported less side-effects than those taking amitriptyline.