2, 3-Dimethoxy-5-methyl-1, 4-benzoquinones having an ω-hydroxyalkyl or ω-aminoalkyl group at the 6-position were synthesized. The effects of these compounds and related compounds on the respiratory system of ubiquinone-depleted mitochondrial preparations were investigated. The compounds with an alkyl side chain of 10 to 13 carbon atoms showed rather high restoration activity on antimycin-sensitive succinate oxidation in acetone-treated beef heart mitochondria. This activity was correlated with their partition coefficients. Among these compounds, 6-(10-hydroxydecyl)-2, 3-dimethoxy-5-methyl-1, 4-benzoquinone (V-10, idebenone) was selected for further testing to determine its effect on the respiratory system of injured canine brain mitochondrial preparation, because this compound showed prominent activity in the system described above. When V-10 was added to acetone-treated canine brain mitochondria (A-CBM), antimycin- and KCN-sensitive succinate oxidation were restored to the level observed in the freeze-stored canine brain mitochondria (CBM). V-10 also restored the reduced nicotinamide adenine dinucleotide (NADH) oxidation of pentane-treated canine brain mitochondria and submitochondrial particles (P-CBM and P-CBSM). Metabolites (I-4, I-10) of V-10 in human and animals showed no restoration activity in either respiratory enzyme system.