To determine whether fenfluramine's anorectic and neurotoxic effects could be dissociated, rats were treated with fenfluramine or the serotonin transporter blocker fluoxetine, alone or in combination. Fenfluramine alone produced anorexia, weight loss and lasting depletions of brain serotonin axon markers. Fluoxetine prevented fenfluramine-induced long-term serotonergic deficits, yet did not diminish fenfluramine's acute anorectic effects. These findings indicate that fenfluramine's anorectic and neurotoxic actions are distinct and separable.