Objective: (R,R,R)-α-tocopherol is a fat-soluble antioxidant vitamin generally ingested with other dietary antioxidants. The objective of this study was to assess whether the main dietary antioxidant classes, that is carotenoids, polyphenols, vitamin C and γ-tocopherol, affect the intestinal absorption of α-tocopherol. Methods, design and subjects: We evaluated first the effect of different combinations of antioxidants on (R,R,R)-α-tocopherol absorption by a human intestinal cell line (Caco-2 clone TC7). Then we compared the effect of two doses of a dietary antioxidant (lutein) on the postprandial chylomicron α-tocopherol responses to an α-tocopherol-rich meal. Eight healthy men ate two similar meals in a random order at a 1 month interval. The meals contained 24 mg α-tocopherol in sunflower oil plus either 18 or 36 mg lutein. Blood samples were collected during the postprandial periods to compare chylomicron α-tocopherol responses. Results: A mixture of polyphenols (gallic acid, caffeic acid, (+)-catechin and naringenin) and a mixture of carotenoids (lycopene, β-carotene and lutein) significantly impaired α-tocopherol absorption in Caco-2 cells (P<0.001 and P<0.0001, respectively). The inhibitory effect of γ-tocopherol was close to significance (P=0.055). In contrast, vitamin C had no significant effect (P=0.158). Naringenin was the only polyphenol that significantly impaired α-tocopherol absorption. Postprandial α-tocopherol response was weakest at the highest dose of lutein (616+/-280 nmol/l h vs 1001+/-287 nmol/l h). The observed extent of reduction (-38%, P=0.069) supported the inhibitory effect of carotenoids observed in the Caco-2 experiments. Conclusion: Naringenin, carotenoids and probably γ-tocopherol can impair α-tocopherol absorption whereas vitamin C and phenolic acids have no effect.