BACKGROUND: An adverse hematological interaction between vitamins E and K has been reported, primarily in patients on anticoagulants. However, little is known regarding circulating levels or tissue concentrations of vitamin K in response to vitamin E supplementation. The purpose of this study was to examine the effect of different levels of dietary alpha-tocopherol on phylloquinone and menaquinone-4 concentrations, while maintaining a constant intake of phylloquinone, in rat tissues. METHODS: Male 4-wk old Fischer 344 rats (n = 33) were fed one of 3 diets for 12 wk: control (n = 13) with 30 mg all-rac-alpha-tocopherol acetate/kg diet; vitamin E-supplemented (n = 10) with 100 mg all-rac-alpha-tocopherol acetate/kg diet; and vitamin E-restricted (n = 10) with <10 mg total tocopherols/kg diet. All 3 diets contained 470 +/- 80 microg phylloquinone/kg diet. RESULTS: Phylloquinone concentrations were lower (P < or = 0.05) in the vitamin E-supplemented compared to the vitamin E-restricted group (mean +/- SD spleen: 531 +/- 58 vs. 735 +/- 77; kidney: 20 +/- 17 vs. 94 +/- 31, brain: 53 +/- 19 vs. 136 +/- 97 pmol/g protein respectively); no statistically significant differences between groups were found in plasma, liver or testis. Similar results were noted with menaquinone-4 concentrations in response to vitamin E supplementation. CONCLUSION: There appears to be a tissue-specific interaction between vitamins E and K when vitamin E is supplemented in rat diets. Future research is required to elucidate the mechanism for this nutrient-nutrient interaction.