Chronic inflammation is a risk factor for many diseases of aging. Endogenous oxidants are thought to mediate the effects of inflammation and gamma-Tocopherol (gamma-Toc) may mitigate damage from nitrogen-based oxidants; however, no physiological requirement for gamma-Toc has been established. Regulation of tocopherols and their functional significance are poorly defined, thereby limiting their application in prevention. Using stored plasma samples from 657 male control subjects in a previous study of prostate cancer, we have analyzed associations of the tocopherols, inflammation markers, and 25-hydroxy (OH) vitamin D. Plasma alpha-Toc and gamma-Toc were inversely correlated, whereas delta-Toc and alpha-Toc levels were positively correlated, suggesting a unique regulatory mechanism. gamma-Toc levels were positively and alpha-Toc negatively associated with plasma C-reactive protein (CRP) and urinary isoprostane F(2t), which are markers of inflammation and oxidation. Ethnic variability in tocopherols was observed; however, this may be explained by differences in plasma 25-OH vitamin D, as gamma-Toc levels varied inversely and alpha-Toc positively with 25-OH vitamin D. In these data, all-cause mortality appeared to be positively associated with CRP and inversely with 25-OH vitamin D. We hypothesize that plasma levels of tocopherols may serve as markers of systemic inflammation, complicating epidemiologic assessment of their role in cancer etiology.