This study was undertaken to evaluate, in humans, the antioxidant activity of olive oil phenolics, namely hydroxytyrosol and oleuropein aglycone that share an orthodiphenolic (catecholic) structure. Human volunteers were administered olive oil samples containing increasing amounts of an olive oil phenolic extract that was characterized by gas-chromatography/mass spectrometry, The administration of phenol-rich oils was dose-dependently associated with a decreased urinary excretion of 8-iso-PGF(2 alpha), a biomarker of oxidative stress. Also, a statistically significant negative correlation between homovanillyl alcohol (HValc, hydroxytyrosol's major metabolite, formed through the COMT system) and F-2-isoprostanes excretion was found. Thus, the administration of oil samples with increasing, albeit low, concentrations of orthodiphenolic compounds, namely hydroxytyrosol and oleuropein aglycone, results in a dose-dependent reduction in the urinary excretion of 8-iso-PGF(2 alpha). The statistically significant negative correlation between 8-iso-PGF(2 alpha) and HValc urinary concentrations suggests that this metabolite better reflects the in vivo activities of hydroxytyrosol,