The clinical efficacy and safety of fluoxetine and imipramine were compared in a double-blind, 5-week, parallel study in 40 depressed outpatients. Mean scores for most depression scales improved more in patients taking fluoxetine than in those receiving imipramine (p less than .05). Nine of 16 (56%) fluoxetine patients who completed the study and 1 of 19 (5%) imipramine patients were not at all depressed at the end of the study (p less than .001). Seven fluoxetine patients and 14 imipramine patients reported one or more adverse effects during treatment; no fluoxetine patient terminated the study early for drug-related reasons. It was concluded that fluoxetine provides effective antidepressant activity with fewer and less troublesome side effects than imipramine.