The aim of the present study was to investigate the effect of adjunctive olanzapine in patients with obsessive-compulsive disorder (OCD) refractory to paroxetine. Twenty-one patients unresponsive to treatment with paroxetine, administered for at least 12 weeks at the dose of 60 mg/day, participated to a 12-week open-label, add-on trial with olanzapine (10 mg/day). The psychopathological state was evaluated by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and by Clinical Global Impression (CGI). Three patients did not complete the 12-week adjunctive treatment with olanzapine. In the 18 completers, the mean Y-BOCS score decreased significantly from 27.1+/-4.0 at baseline to 20.1+/-3.9 at final evaluation (P<.001). Seven patients (38.9%) were rated as responders at final evaluation. Steady-state plasma concentrations of paroxetine were not modified during olanzapine coadministration. The drug combination was generally well tolerated and initial sedation and weight gain were the most frequent unwanted effects. Our findings confirm the results of previous studies and indicate that the addition of olanzapine to ongoing treatment with serotonin reuptake inhibitors (SRI) may be beneficial in some patients unresponsive to SRI monotherapy.