It has recently been shown that bromobenzene is converted to multiple reactive metabolites. However, the nature of these reactive metabolites is unclear. In the present manuscript, we have demonstrated that the same cytochromes P-450 activate both bromobenzene and p-bromophenol, and each substrate competitively inhibits the metabolism of the other. Moreover, the covalent binding of p-bromophenol to rat liver microsomes was inhibited by epoxide hydrolase, catechol-O-methyltransferase, superoxide dismutase, glutathione, and ascorbic acid but not by catalase. In contrast, the amount of 4- bromocatechol isolated from microsomal incubations containing p-bromophenol was decreased by glutathione and increased by ascorbic acid and superoxide dismutase. It is thus likely that p-bromophenol is converted to an epoxide that decomposes to 4- bromocatechol and that both the epoxide and the quinone formed from oxidation of 4- bromocatechol may become covalently bound to tissue proteins. However, these chemically reactive metabolites are apparently nontoxic because treatments which increase the covalent binding of p-bromophenol in vitro do not cause toxicity in vivo.