Previous studies have not agreed on the incidence of ischemic stroke in persons with Parkinson's disease. There are epidemiologic and neurochemical facets of Parkinson's disease that might confer some benefit or protection against ischemic stroke. We used a case-control method to determine the lifetime history of ischemic stroke in 200 patients with Parkinson's disease and 200 controls of a similar age range. Analysis was also carried out for myocardial infarction as a marker of generalized atherosclerotic disease and for stroke risk factors. The cumulative incidence of ischemic stroke was significantly less in the patients with Parkinson's disease than in the controls, as was the cumulative incidence of myocardial infarction. Among risk factors, significantly fewer patients with Parkinson's disease used tobacco than controls. The decreased incidence of ischemic stroke in the patients with Parkinson's disease appears to be related to their less severe generalized atherosclerosis, possibly due to their lower incidence of tobacco use. In view of the known potential for dopamine to exacerbate experimental ischemic tissue damage, the possibility that the dopamine deficiency in the central nervous system of persons with Parkinson's disease confers an additional specific protective benefit against ischemic stroke cannot be excluded and requires further study.