Since their introduction, atypical neuroleptic agents have been discovered to have some beneficial effects beyond their effectiveness as neuroleptic drugs. Among these initially unexpected effects are their potential effects as mood stabilizers in bipolar disorder and their efficacy in improving long-term outcome in schizophrenia. These effects recently raised the question whether these drugs may also have some neuroprotective effect in the brain. To examine this matter, in this study we evaluated the neuroprotective effect of risperidone after permanent focal cerebral ischemia. Anaesthetized male C57BL/6j mice were submitted to permanent thread occlusion of the middle cerebral artery (MCA). Risperidone (0.1, 1 or 10 mg/kg) or vehicle was applied intraperitoneally just after permanent ischemia. Twenty-four hours after permanent ischemia, brain injury was evaluated by triphenyltetrazolium chloride staining (TTC). Risperidone (0.1, 1 and 10 mg/kg) showed significant neuroprotection after permanent focal cerebral ischemia.