Cytochrome P450-mediated metabolism ofN-(2-methoxyphenyl)-hydroxylamine, a human metabolite of the environmental pollutants and carcinogenso-anisidine ando-nitroanisoleN-(2-methoxyphenyl)hydroxylamine is a human metabolite of the industrial and environmental pollutants and bladder carcinogens 2-methoxyaniline (o-anisidine) and 2-methoxynitrobenzene (o-nitroanisole). Here, we investigated the ability of hepatic microsomes from rat and rabbit to metabolize this reactive compound. We found thatN-(2-methoxyphenyl)hydroxylamine is metabolized by microsomes of both species mainly too-aminophenol and a parent carcinogen,o-anisidine, whereas 2-methoxynitrosobenzene (o-nitrosoanisole) is formed as a minor metabolite. AnotherN-(2-methoxyphenyl)hydroxylamine metabolite, the exact structure of which has not been identified as yet, was generated by hepatic microsomes of rabbits, but its formation by those of rats was negligible. To evaluate the role of rat hepatic microsomal cytochromes P450 (CYP) inN-(2-methoxyphenyl)hydroxylamine metabolism, we investigated the modulation of its metabolism by specific inducers of these enzymes. The results of this study show that rat hepatic CYPs of a 1A subfamily and, to a lesser extent those of a 2B subfamily, catalyzeN-(2-methoxyphenyl)hydroxylamine conversion to form both its reductive metabolite,o-anisidine, ando-aminophenol. CYP2E1 is the most efficient enzyme catalyzing conversion ofN-(2-methoxyphenyl)hydroxylamine too-aminophenol.