1. Twelve patients with borderline personality disorder and not suffering a major depression were treated with fluoxetine, a selective serotonin reuptake inhibitor, in an open label trial. All of the patients improved, and 75% were rated as much or very much improved. 2. Treatment was generally very well tolerated, but careful dosage titration was important in some patients, especially to manage agitation. 3. Improvement has been maintained with continued treatment throughout the follow-up period which ranged up to six months. 4. Incidental findings suggest fluoxetine may also be of use in treating substance abuse, attention deficit hyperactivity disorder, late luteal phase dysphoria disorder, dysthymic and cyclothymic disorders, and seasonal pattern depression. 5. These preliminary results support the hypothesis that borderline personality disorder may be related to a central serotonergic deficit.