Coenzyme Q (CoQ) was previously demonstrated in vitro to indirectly act as an antioxidant in respiring mitochondria by regenerating alpha-tocopherol from its phenoxyl radical. The objective of this study was to determine whether CoQ has a similar sparing effect on alpha-tocopherol in vivo. Mice were administered CoQ10 (123 mg/kg/day) alone, or alpha-tocopherol (200 mg/kg/day) alone, or both, for 13 weeks, after which the amounts of CoQ10, CoQ9 and alpha-tocopherol were determined by HPLC in the serum as well as homogenates and mitochondria of liver, kidney, heart, upper hindlimb skeletal muscle and brain. Administration of CoQ10 and alpha-tocopherol, alone or together, increased the corresponding levels of CoQ10 and alpha-tocopherol in the serum. Supplementation with CoQ10 also elevated the amounts of the predominant homologue CoQ9 in the serum and the mitochondria. A notable effect of CoQ10 intake was the enhancement of alpha-tocopherol in mitochondria. alpha-Tocopherol administration resulted in an elevation of alpha-tocopherol content in the homogenates of nearly all tissues and their mitochondria. Results of this study thus indicate that relatively long-term administration of CoQ10 or alpha-tocopherol can result in an elevation of their concentrations in the tissues of the mouse. More importantly, CoQ10 intake has a sparing effect on alpha-tocopherol in mitochondria in vivo.