Data from a pilot study suggest that naltrexone might reduce dissociative symptoms in patients with borderline personality disorder. However, the interpretation of these data is limited by the lack of a control group and by the nonblind nature of this study. Hence, we examined the effects of naltrexone using a more rigorous design that controlled for major confounders such as spontaneous reduction of dissociation over time and placebo effects. Unmedicated patients with BPD [according to Diagnostic and Statistical Manual of Mental Disorders-IVth edition (DSM-IV)] were included in two small double-blind placebo-controlled randomized trials (total n=29). Patients received both 3 weeks of naltrexone (50 or 200 mg/day) and 3 weeks of placebo in a randomized order. Twenty-five patients completed the study according to protocol. Dissociation under naltrexone and placebo, respectively, was compared by repeated-measures analyses of variance. In either trial, both the intensity and duration of dissociative symptoms were numerically lower under naltrexone than under placebo. However, the effects were too small to reach statistical significance. Our data provide the first estimate of the pure pharmacological antidissociative efficacy of naltrexone from a rigorously designed trial.