The prevalence of tardive dyskinesia (TD) in chronic psychiatric outpatients was significantly higher in smokers (46/85) than in nonsmokers (18/69) (p less than 0.001). This increased prevalence was associated with a significantly greater prescribed dose of neuroleptics in women, but not in men. Nicotine increases the synthesis and release of dopamine in the nigrostriatal pathway of animals. Such a mechanism may contribute to the higher prevalence of TD in smokers. The present findings suggest that smoking is a risk factor for the development of TD. A statistically significant association between smoking and TD, however, does not necessarily imply a cause-effect relationship. Treatment of TD with mecamylamine or other central nicotine antagonists merits investigation.