NADPH oxidases (NOX) are a major source of superoxide formation in renal epithelia and intrarenal vessels. Rat intrarenal arteries express NOX1, NOX2, and NOX4 while human intrarenal arteries express only NOX2 and NOX4. In vitro administration of superoxide scavengers to rat and human proximal renal resistance vessels do not significantly affect adrenoceptor agonist- and endothelin-1-induced vasoconstrictions. Superoxide anions have a short half life and elicit cellular actions in close proximity to the site of their formation. They are converted to hydrogen peroxide which has a high cellular permeability and exerts paracrine actions. In the rat and human renal circulation hydrogen peroxide elicits vasoconstriction. The susceptibility of intrarenal vessels to hydrogen peroxide-induced constrictions increases after a₁-adrenoceptor stimulation. Excess renal superoxide formation contributes to the pathogenesis of hypertension. The early phase of hypertension development can be conveniently studied in transgenic rats carrying an inducible renin transgene. The transgene-induced rise in blood pressure is preceded by increased NOX- dependent superoxide formation in intrarenal arteries. The increased superoxide formation is associated with elevated renal vascular resistance, exaggerated sensitivity to hydrogen peroxide-induced vasoconstriction and increased Rho-kinase dependence of a₁- adrenoceptor-mediated vasoconstriction. Endothelium-dependent vasodilation and the sensitivity of the renal vasculature to a₁-adrenoceptor or AT₁ receptor stimulation are not affected. These data suggest that NOX-dependent superoxide formation in small intrarenal arteries is less important for acute agonist-induced vascular responses but may play a major role for the long-term regulation of renal vascular resistance, in particular when the sympathetic nervous system or the renin-angiotensin system are chronically stimulated.