Fluoxetine is a new, chemically unique antidepressant. In contrast with antidepressants already on the market, its only significant neurophysiologic effect is inhibition of serotonin reuptake. Double-blind comparisons show it is as effective in the treatment of major depression as tricyclic antidepressants. It is free of most of the troubling side effects of currently available antidepressants, including anticholinergic effects and weight gain. In fact, it is commonly associated with weight loss which is independent of nausea, the most commonly reported adverse effect. The recommended dose is 20 mg per day, given in the morning or early in the day. Fluoxetine deserves consideration for depressed patients for whom the clinician wishes to avoid anticholinergic effects, sedation, and weight gain. It may be especially effective in patients with pronounced obsessive-compulsive symptoms, weight gain with depression or from antidepressants, and in patients who have not responded to tricyclic therapy.