Background; We previously demonstrated that an NAD(P)H oxidase plays an important role in blood pressure (BP) elevation, cardiovascular hypertrophy, and fibrosis in aldosterone-infused rats. The functional role of the different subunits of the enzyme to target organ damage is still not understood. We evaluated whether the p47phox is implicated in BP elevation and cardiovascular dysfunction using p47phox deficient mice. Methods and Results; Male mice lacking p47phox (p47phox-/-) and wild-type (WT) C57BL/6 mice of 12 months of age were infused with aldosterone (0.25 µL/h for 2 weeks) via a mini-osmotic pump and were given as treated0.9 % NaCl in the drinking water +/- an aldosterone receptor antagonist, spironolactone (200���/��� per day). Systolic BP (SBP) was measured by tail-cuff method. The activity of NAD(P)H oxidase was assessed by lucigenin-enhanced chemiluminescent detection. Vascular structural and functional changes of mesenteric arteries were evaluated using a pressurized myograph. Aldosterone infusion (0.75 關g/h for 14 days) increased systolic BP from 944 to 1417 mmHg and increased vascular O2- production in wild-type (WT) mice. In contrast, in p47phox-/- mice, systolic blood pressure and vascular O2- production were unchanged. Media/lumen ratio, a marker of vascular structural remodeling, was increased and acetylcholine-mediated relaxation, a marker of endothelial function, was impaired in mesenteric small arteries from aldosterone-infused WT mice, which was not found in aldosterone-infused p47phox-/- mice. Conclusions; There results suggest a pivotal role of the NAD(P)H oxidase subunit, p47phox, in cardio-renal and vascular damage in aldosterone-infused hypertension.