Superoxide anions react with nitric oxide to form peroxynitrite and hence reduce the bioavailability of nitric oxide in the arteries. Extracellular superoxide dismutase (EC-SOD) is a major superoxide scavenger in human plasma and vascular tissues. The objective of this study is to assess whether essential hypertension is associated with an alteration in EC-SOD activity. In this report, blood samples were obtained from hypertensive (n=39) and normotensive (n=37) African-Americans. Plasma EC-SOD activity was measured using in-gel activity staining and spectrophotometric assays, EC-SOD protein level was measured using Western blotting, nitrotyrosine was measured using slot blotting, 8-isoprostane was measured with an enzyme immunoassay, and plasma copper and zinc concentrations were measured using an atomic absorption assay. Our data demonstrate that the copper, zinc, and plasma EC-SOD protein concentrations in the hypertensive and normotensive subjects are indistinguishable. Compared to normotensive controls, hypertensive patients have significantly reduced plasma EC-SOD activity. Plasma nitrotyrosine and 8-isoprostane levels are significantly higher in the hypertensive patients than in normotensive controls. Results from this study suggest that a reduction in EC-SOD activity in hypertensive patients is not due to a down-regulation of the SOD3 gene (encoding EC-SOD) or deficiency in mineral cofactors. Furthermore, the reduced EC-SOD activity might be at least partially responsible for the increased oxidative stress, as reflected by increased plasma nitrotyrosine and 8-isoprostane, in hypertensive subjects.