The present study was designed to test the hypothesis that blockade of angiotensin II type-1 receptors reduces oxidative stress and inflammation in patients with essential hypertension. The study population comprised 132 hypertensive patients, some receiving and others not receiving medical treatment. At enrollment their systolic and/or diastolic blood pressures were ≥140 and/or ≥90 mmHg, respectively. The serum concentration of C-reactive protein, and the urine concentrations of 8-epi-prostaglandin F_2α and 8-hydroxydeoxyguanosine were measured at baseline and after 12 weeks of treatment either with an angiotensin II type-1 receptor blocker, candesartan (8 mg daily) (age 64±12 years; male/female 28/39; n =67), or other antihypertensive agents that do not block the renin-angiotensin system (age 65±10 years, male/female 25/40, n =65). Candesartan reduced the levels of C-reactive protein (from 0.07±0.04 [median value ± median absolute deviation] to 0.06±0.03 mg/dl, p <0.0001), 8-epi-prostaglandin F_2α (from 210±92 to 148±59 pg/mg creatinine, p <0.0001), and 8-hydroxydeoxyguanosine (from 5.7±1.9 to 4.0±1.3 ng/mg creatinine, p <0.0001), while the levels of these markers were not altered after the treatment with other antihypertensive agents. Blood pressure decreased by a similar amount in both groups, and the reductions in the levels of the markers did not correlate with that of blood pressure. These results suggest that candesartan reduces oxidative stress and inflammation in hypertensive patients independently of its effects on blood pressure. This may provide useful information for determining therapeutic strategies to minimize tissue injury by inflammation and oxidative stress in hypertensive patients. (Hypertens Res 2003; 26: 691-697)