This study tested the hypothesis that acute reduction in blood pressure (BP) at the initial stage of antihypertensive therapy compromises brain perfusion and dynamic cerebral autoregulation in patients with hypertension. Cerebral blood flow velocity and BP were measured in patients with mild and moderate hypertension and in healthy volunteers at baseline upon reduction of BP within 1 to 2 weeks of administration of losartan/hydrochlorothiazide and after 3 to 4 months of treatment. The transfer function between beat-to-beat changes in BP and cerebral blood flow velocity was estimated to assess dynamic autoregulation. After 1 to 2 weeks of treatment, BP was reduced in mild (143+/-7/88+/-4 versus 126+/-12/77+/-6 mm Hg) and moderate hypertension (163+/-11/101+/-9 versus 134+/-17/84+/-9 mm Hg; P<0.05). These reductions in BP were well maintained over the 3 to 4 month period. Cerebral blood flow velocity did not change, whereas cerebrovascular resistance index was reduced by 17% (P<0.05) after reduction in BP. Responses of cerebral blood flow velocity to head-up tilt remained unchanged. Baseline transfer function gain at the low frequencies (0.07 to 0.20 Hz) was reduced in moderate hypertension, consistent with cerebral vasoconstriction and/or enhanced dynamic autoregulation. However, this reduced transfer function gain was restored to the level of control subjects after reduction in BP. These findings, contrary to our hypothesis, demonstrate that there is a rapid adaptation of the cerebral vasculature to protect the brain from hypoperfusion even at the initial stage of antihypertensive therapy in patients with mild and moderate hypertension.