An open-label trial was performed to explore efficacy and safety of olanzapine, an atypical neuroleptic with diverse receptor activity including both dopamine-2 and serotonin-2A and -2C antagonism, for treatment of Tourette's disorder. Ten adult patients aged 20 to 44 years with Tourette's disorder were treated using an open-label, flexible dosing schedule for 8 weeks. Three patients who continued olanzapine were reevaluated after 6 months. Three subjects were psychotropic medication naive, 5 patients experienced intolerable side effects with conventional neuroleptics, and 2 patients had remote (> or = 10 years) successful response to conventional neuroleptics. Tic severity was rated by the Yale Global Tic Severity Scale; weight, vital signs, and adverse effects were assessed weekly. Electrocardiogram, laboratory studies, and comorbid symptoms, assessed by the Yale-Brown Obsessive Compulsive Scale and ADHD Behavior Checklist for Adults, were measured at baseline and at week 8. Two of 10 patients prematurely discontinued olanzapine owing to excessive sedation. Of 8 patients who completed the 8-week trial, 4 (50%) demonstrated reduction of global tic severity scores by > or = 20 points, and 6 (75%) demonstrated reductions by > or = 10 points. No significant changes in comorbid symptoms were demonstrated. Sedation, weight gain, increased appetite, dry mouth, and transient asymptomatic hypoglycemia were the most common side effects. Tic improvements were maintained in 3 patients reassessed 6 months later. Final olanzapine dosages ranged from 2.5 mg to 20 mg daily (mean = 10.9 mg/day). This open-label study suggests that olanzapine should be explored as a potential alternative to conventional neuroleptic medications for treatment of motor tics and Tourette's disorder.