The role of human cytochrome P-450 IIEl (P-450 IIEl) in the oxidation of a number of suspect carcinogens was examined by using a variety of approaches, including (1) selective inhibition of catalytic activity in human liver microsomes by diethyldithiocarbamate, which was found to be a selective mechanism-based inactivator of P-450 IIEl,(2) correlation of rates of different catalytic activities with each other and with chlorzoxazone 6-hydroxylation, an indicator of P-450 IIEl, in human liver microsomes,(3) demonstration of catalytic activity in reconstituted systems containing purified human P-450 IIEl, and (4) immunoinhibition of catalytic activity in human liver microsomes with rabbit anti-human P-450 IIEl. The results collectively indicate that P-450 IIEl is a major catalyst of the oxidation of benzene, styrene, CC14, CHC13, CH2C12, CH3C1, CH3CC13, 1, 2-dichloropropane, ethylene dichloride, ethylene dibromide, vinyl chloride, vinyl bromide, acrylonitrile, vinyl carbamate, ethyl carbamate, and trichloroethylene. Levels of P-450 IIEl can vary considerably among individual humans—the availability of chlorzoxazone as a noninvasive probe of human P-450 IIEl and of disulfiram (oxidized diethyldithiocarbamate) as an inhibitor may facilitate discernment of the in vivo significance of human P-450 IIEl as a factor in the bioactivation and detoxication of these cancer suspects. Further, manyinves-tigations with diethyldithiocarbamate, disulfiram, and ethanol in humans and experimental animals may be interpreted in light of mechanisms involving P-450 IIEl.