DT-diaphorase catalyzes the two-electron reduction of the unsubstitutted quinone epoxide, 2,3-epoxy- p-benzoquinone, at expense of NAD(P)H with formation of 2-OH- p-benzohydroquinone the reaction product. The further conversion reactions of 2-OH- p-benzohydroquinone are in fluenced by the presence of O 2 in the medium. Under aerobic conditions, 2-OH- p-benzohydroquinone undergoes autoxidation-probably with formation of 2-OH-semiquinone intermediates-to 2-OH- p-benzoquinone. The latter product is rapidly reduced by DT-diaphorase and, thus, its accumulation can be only observed upon exhaustion of NADPH. Under anaerobic conditions, 2-OH- p-benzohydroquinone does not undergo autoxidation and its accumulation is stoichiometrically (1:1) related to the amount of NADPH oxidized and epoxide substrate reduced. DT-diaphorase also catalyzes the reduction of the disubstituted quinone expoxide, 2,3-dimethyl-2,3-epoxy-1,4-naphtoquinone. Neither the aliphatic epoxide, trans-stilbene oxide, nor the aromatic epoxide, 4,5-epoxy-benzo[a]pyrene are substrates for DT-diaphorase. The reduction of 2,3-epoxy- p-benzoquinone is also catalyzed by the one-electron transfer enzyme, NADPH-cytochrome P450 reductase at a rate similar to that found with DT-diaphorase. However, this reaction differs from that catalyzed by DT-diaphorase in the distribution of molecular products as well as in the relative contribution on nonenzymatic reactions, i.e. semiquinone disproportiona and autoxidation.