Vitamin E (VE) and coenzyme Q (CQ) are essential for maintaining functions and integrity of mitochondria, and high concentrations of these compounds are found in their inner membranes. This study was conducted to examine the interaction between exogenously administered CQ10 and VE in rats. Male Sprague-Dawley rats (12 mo old) were fed a basal diet (10 IU VE or 6.7 mg RRR-alpha-tocopherol equivalent) supplemented with either 0 or 500 mg CQ10, and 0, 100 or 1310 IU VE/kg diet for 14 or 28 d. Liver, spleen, heart, kidney, skeletal muscle, brain and serum were analyzed for the levels of CQ10, CQ9 and VE. CQ10 supplementation significantly (P: < 0.05) increased CQ10 concentration in the liver and spleen (total and mitochondria) and serum, but not in other organs. Interestingly, rats supplemented with CQ10 plus 100 IU VE/kg diet had significantly higher CQ10 levels in the liver and spleen, whereas those supplemented with CQ10 plus 1310 IU VE/kg diet had lower levels, compared with those supplemented with CQ10 alone. As expected, dietary VE increased VE content in all of the organs analyzed in a dose-dependent manner. However, rats fed the basal diet supplemented with CQ10 had significantly higher VE levels in liver (total and mitochondria) than those not receiving CQ10 supplementation. CQ9 levels were higher in the liver and spleen, lower in skeletal muscle and unaltered in brain, serum, heart and kidney of rats supplemented with CQ10 compared with the controls. These data provide direct evidence for an interactive effect between exogenously administered VE and CQ10 in terms of tissue uptake and retention, and for a sparing effect of CQ10 on VE. Data also suggest that dietary VE plays a key role in determining tissue retention of exogenous CQ10.