Lipophilic o-naphthoquinones (beta-lapachone, CG 8-935, CG 9-442, CG 10-248, and mansonones A, C, E, and F), catalyze the oxidation of dihydrolipoamide (DHLA) by oxygen, whereas p-naphthoquinones (alpha-lapachone and menadione) are scarcely active. The greatest effects corresponded to beta-lapachone and its analogues. Quinol production was demonstrated by (a) the absorption spectrum of the reduced quinone, and (b) the effect of pH variation on the rate of quinone-catalyzed DHLA oxidation. Superoxide dismutase (SOD) inhibited the rate of cytochrome c reduction and decreased the apparent rate of oxygen consumption by several DHLA/o-naphthoquinone systems. SOD also inhibited the rate of quinol oxidation by oxygen, after quinone reduction by a stoichiometric amount of DHLA. Catalase enhanced the effect of SOD, but in its absence catalase was inactive. It is concluded that quinone-catalyzed oxidation of DHLA implies a free-radical mechanism in which the quinol and superoxide radicals play an essential role.