Background: C-reactive protein (CRP) predicts cardiovascular outcome. Oxidative stress is considered to be involved in endothelial alteration. We hypothesized that in essential hypertension (EH), oxidative stress, as measured by 8-iso-prostaglandin-F-2 alpha (8-iso-PGF(2 alpha)), should be associated with increased CRP and endothelial activation, as evaluated by soluble intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) plasma levels. Methods: In 83 subjects with mild EH and in 50 healthy control subjects we measured, in basal conditions, plasma levels of hs-CRP, 8-iso-PGF(2 alpha), ICAM-1 and VCAM-1, and tumor necrosis factor-alpha (TNF-alpha). Results: Subjects with EH had higher levels of 8-iso-PGF(2 alpha) (P <.0001), CRP (P <.001), ICAM-1 and VCAM-I (P <.001), and TNF-alpha (P <.001) than did control subjects. We divided successively EH according to CRP values (<1, 1-3, >3 mg/L), and we observed increasing and significantly different levels of the endothelial parameters and of TNF-alpha along with increasing CRP. Linear analysis of correlation pointed out significant correlation of CRP with 8-iso-PGF(2 alpha) (r = 0.730, P <.001), ICAM-1 and VCAM-1 (r = 0.642 and 0.468, P <.001 respectively), and TNF-alpha (r = 0.609, P <.001). Multiple regression analysis using CRP as a dependent variable confirmed the relationship of CRP with systolic blood pressure (beta 0.216, P = 0.039) and with 8-iso-PGF(2 alpha) (beta 0.602, P =.0001). Conclusions: Our data demonstrate that in EH, inflammatory molecules such as CRP and TNF-alpha are increased and related to both oxidative stress and endothelial activation.