Calcium channel blockers have been widely used for the treatment of hypertension because several clinical trials have demonstrated their strong action on lowering blood pressure and their role in preventing cardiovascular events such as stroke and coronary heart disease. However, there have been few reports on the effects on cerebral hemodynamics when blood pressure is lowered with this class of drug. In this study, we used positron emission tomography and acetazolamide challenge tests to measure cerebral blood flow and cerebrovascular reserve before and after administration of a novel calcium channel blocker, azelnidipine, in nine hypertensive patients (mean age, 66.1 years) with ischemic white matter lesions. Systemic blood pressure was significantly decreased from baseline (153.8+/-15.5/92.1+/-8.5 mmHg) after treatment with azelnidipine (138.4+/-16.3/81.8+/-6.2 mmHg). The baseline global cerebral blood flow values before and after treatment were 40.1+/-7.2 mL/min/100 g and 39.2+/-8.2 mL/min/100 g, respectively. The cerebrovascular reserve values before and after treatment were 58.6+/-21.7% and 56.3+/-21.3%, respectively. Differences in these parameters were not significant. A regional analysis showed no statistical differences in regional cerebral blood flow or cerebral perfusion reserve throughout the brain before and after treatment. No associations between the decreased blood pressure and the changes in cerebral blood flow or cerebrovascular reserve were found in the whole brain or in the deep white matter with ischemic lesions. In conclusion, we found that the cerebral blood flow and cerebral vascular reserve were preserved after blood pressure lowering with azelnidipine administration in hypertensive patients with ischemic white matter lesions. Azelnidipine, a novel calcium channel blocker, could be a feasible antihypertensive regimen in terms of cerebral circulation in patients with ischemic white matter lesions.