Borderline personality disorder (BPD) is defined by many of the symptoms associated with serotonin dysregulation, including affective lability, suicidal behaviors, and impulsive aggression, providing an ideal clinical model for studying the treatment of these serious disorders. The recent development of selective serotonin re-uptake inhibitors such as fluoxetine makes it possible to study the role of serotonin in the etiology of affective and behavioral dyscontrol in BPD. In this preliminary medication trial, 5 patients with BPD were treated openly with 20 mg to 40 mg of fluoxetine for 8 weeks, with weekly ratings of symptoms. The findings from this work suggested efficacy for fluoxetine in treating the depressive and impulsive symptoms of patients with BPD. The findings were mixed concerning the efficacy of fluoxetine in treating the hostility and psychotic symptoms of BPD. No evidence for effectiveness was found in the treatment of the anxiety, phobic anxiety, or interpersonal sensitivity of BPD.