Hypertension appears to alter brain morphology, as well as the cerebrovascular support for information processing. Because these effects might reflect progressive effects of essential hypertension on the brain, we asked whether structural and functional brain indices would predict the success of pharmacological treatment of hypertension among 45 previously unmedicated individuals. After initial structural MRI and functional positron emission tomography imaging, subjects were randomly assigned in a double-blind fashion for treatment for 1 year with either lisinopril or atenolol. Systolic and diastolic blood pressure decreases after treatment stabilization were correlated to a pretreatment index of brain aging (combined ratings of ventricle and sulcal size and white matter hyperintensities) and the pretreatment change in regional cerebral blood flow during working memory in the thalamus and posterior parietal regions of interest. In multiple regression analyses, the structural brain index and the blood flow response in the thalamus predicted 20% of the variance in the systolic blood pressure response to treatment controlling for pretreatment blood pressure, age, gender, and type and dose of medication. Alcohol use influenced the thalamic response measure, but covariates did not alter the relation between greater indices of brain aging and less successful blood pressure response to treatment. The state of the brain may be an important factor in the remediation of blood pressure.