Acetaminophen may be converted to chemically reactive metabolites by either horseradish peroxidase and H2O2 or cumene hydroperoxide and hamster microsomes. Moreover, acetaminophen rapidly converts complex II of horseradish peroxidase to its native form indicating that acetaminophen can be oxidized by a one electron system. Whether the formation of the chemically reactive metabolite of acetaminophen formed by NADPH and hamster liver microsomes occurs by a peroxidase-like mechanism remains to be determined.