Inflammation and oxidative stress are processes that mark early metabolic abnormalities in vascular diseases. We explored the effects of a high-fat, high-cholesterol (HFHC) diet on vascular responses in baboons and the potential response-attenuating effects of vitamin E and coenzyme Q(10) (CoQ(10)) supplementation. We used a longitudinal design by subjecting 21 baboons (Papio hamadryas) to sequential dietary challenges. After being maintained for 3 mo on a baseline diet (low in fat and cholesterol), 21 baboons were challenged with an HFHC diet for 7 wk. The serum C-reactive protein (CRP) concentrations did not change. Subsequent supplementation of the HFHC diet with the antioxidant vitamin E (250, 500, or 1000 IU/kg diet) for 2 wk reduced serum CRP concentrations from 0.91 +/- 0.02 to 0.43 +/- 0.06 mg/dL. Additional supplementation with CoQ(10) (2 g/kg diet) further reduced serum CRP to approximately 30% of baseline (0.28 +/- 0.03 mg/dL; P = 0.036 compared with the HFHC diet). Introduction of the HFHC diet itself significantly decreased serum P-selectin (from 48.8 +/- 7.2 to 32.9 +/- 3.7 ng/dL, P = 0.02) and von Willebrand factor (from 187.0 +/- 10.1 to 161.9 +/- 9.0%, P = 0.02) concentrations. However, neither vitamin E alone nor vitamin E plus CoQ(10) significantly altered the serum concentrations of P-selectin or von Willebrand factor. Dietary supplementation with vitamin E alone reduces the baseline inflammatory status that is indicated by the CRP concentration in healthy adult baboons. Cosupplementation with CoQ(10), however, significantly enhances this antiinflammatory effect of vitamin E.