BACKGROUND: The use of atypical antipsychotics in the clinical practice of BPD is increasing, and the literature supporting their effectiveness is small but growing. This article reports the results of a double-blind, placebo-controlled study of olanzapine for BPD. METHODS: Forty patients with BPD (25 women, 15 men) were randomized equally to receive olanzapine and placebo treatment. Diagnoses were made using the Structured Clinical Interview for DSM (SCID) and the Mini-International Neuropsychiatric Interview, a diagnostic and statistical manual for psychiatric disorders for DSM-IV axis IIPDs. Exceptions were schizophrenia, bipolar disorder, or current major depressive disorder. Olanzapine doses were variable, ranging from 2.5 to 20 mg/day, with the vast majority between 5 and 10 mg/day. No combination of psychotropic medications was allowed. Patients were assessed at baseline and at 2, 4, 8 and 12 weeks. The primary outcome measured was change in total score on the 9 BPD criteria from the 1 to 7 Likert scale and the Clinical Global Impressions scale modified for borderline personality disorder (CGI-BPD), with baseline scores used as covariates for analysis of covariance. Data were collected for the period July 2000 to April 2002. RESULTS: The CGI-BPD score was significantly better in the olanzapine group than in the placebo group at the end of the study (p < .05), with a difference visible at the previous 4 weeks. the CGI single-item results were similar. Weight gain was significantly greater in the olanzapine group (p =.027). CONCLUSION: The results of this study support the effectiveness of olanzapine in treating a mixed sample of men and women with BPD. Further studies are needed to compare olanzapine with other atypical antipsychotics.