Animal studies have suggested that the reduction in stroke risk observed with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) therapy is owing to an increase in basal cerebral blood flow (CBF). The purpose of the study was to determine if statin therapy was associated with increased CBF in humans with cerebrovascular atherosclerotic disease. Quantitative measurements of CBF were obtained on study entry in 97 patients with carotid artery occlusion enrolled in a prospective study of cerebral hemodynamics and stroke risk. This study represents a post hoc analysis of CBF measurements based on whether patients were receiving statin therapy at the time of CBF measurement. Global and regional CBF (including hemispheric, basal ganglia, and arterial borderzones), and baseline clinical, epidemiologic, and laboratory stroke risk factors were compared between the two groups. Nineteen of the 97 patients were on a statin agent on study entry. The statin group was younger, had significantly lower LDL levels and included more women. Statin therapy was not associated with higher baseline values of CBF in global or regional analyses. Mean middle cerebral artery territory CBF (+/-s.d.) ipsilateral to the occluded carotid artery was 37.6+/-12.7 mL/100 g min for the statin group (n=19) compared with 38.6+/-12.7 mL/100 g min for the nonstatin group (n=78). Contralateral values were 42.9+/-13.5 and 44.2+/-13.3 mL/100 g min for the statin and nonstatin groups, respectively. We conclude that the stroke risk reduction observed with statin therapy in humans likely involves mechanisms other than an increased basal CBF.