The effects of both opiate agonists and the opiate antagonist naloxone were examined in a rodent model of tardive dyskinesia (TD). Chronic (approximately 20 weeks) administration of fluphenazine resulted in the emergence of vacuous chewing mouth movements (VCMs), a response which may be a useful model for this disorder. Fluphenazine-induced VCMs were not affected by a variety of selective opiate agonists administered intracerebroventricularly, but were potently suppressed by subcutaneous administration of the opiate antagonist naloxone. These findings suggest that increased opiate transmission may contribute to the pathogenesis of TD. Further investigation of the role of opiate antagonists in treating this disorder are warranted.