Diabetes and hypertension are potent risk factors for cerebrovascular disease. We studied the effects of an angiotensin II type 1 receptor blockade (ARB) on brain damage in hypertensives in relation to diabetes. We studied cerebral metabolism (by proton magnetic resonance spectroscopy) and hemodynamics (by phase-contrast magnetic resonance angiography) before and 3 to 4 months after candesartan therapy in 20 diabetic hypertensives (DHTs) and 20 matched nondiabetic hypertensives (HTs). Silent multiple cerebral infarcts detected by brain MRI were more common in DHTs than in HTs (50% versus 25%). Cerebral N-acetyl aspartate (NAA; an indicator of functional neuronal mass) was lower in DHTs than in HTs (8.35 versus 9.58 mmol/kg; P=0.007). Baseline quantitative volume flow in the internal carotid arteries (ICAs) and the middle cerebral arteries (MCAs) was comparable between the 2 groups, whereas cerebrovascular reserve (CVR) assessed using acetazolamide (a cerebral arteriolar dilator) in ICAs (25% versus 35%; P=0.03) and MCAs (20% versus 31%; P=0.01) was lower in DHTs than in HTs. These baseline CVR and NAA values of DHT group were lower than those of 12 matched normotensives (CVR: 44% for ICA; 41% for MCA; NAA: 10.5 mmol/kg; all P<0.005). After candesartan therapy, CVR in ICAs and MCAs was significantly increased (P=0.001) independently of the reduction of the 24-hour blood pressure level, whereas the cerebral NAA level did not change. In conclusion, brain damage is advanced in DHTs. ARB partly improved the impaired cerebral microvascular function in DHTs.