This study shows fluoxetine to be a potent anorectic agent in non-depressed clinically overweight individuals. It is as effective an anorexic compound as a currently available appetite control agent, benzphetamine, and highly significantly more effective than the placebo treatment. A relative lack of serious side-effects and a low abuse potential make it an interesting drug in the slim armamentarium of agents that are used to treat the overweight. If the lack of tolerance to the effects of this drug seen in the long-term studies of depression is confirmed in long-term studies of obese patients, fluoxetine may have a major part to play in the treatment of the obese patient where weight loss is medically indicated. This would include the morbidly obese, the type II diabetic, and the hypertensive patient. Although ideally behavior modification should accompany the drug treatment for obesity, clinical practice indicates that in many cases, patients will not follow through with the behavioral treatment. A strictly medical prescription of an acceptable pharmacologic agent like fluoxetine on a chronic or long-term basis may provide a new possibility for the treatment of these individuals.