Benzo(a)pyrene 4,5-oxide was metabolized in the isolated perfused rat liver by epoxide hydrase and glutathione S-transferases to the corresponding dihydrodiol and to thioether conjugates (derivatives of glutathione), respectively. Epoxide hydrase was more important relative to the glutathione S-transferases in the biotransformation of this oxide by the intact organ than was indicated from earlier studies with subcellular fractions. The dihydrodiol was rapidly released into the circulation or conjugated with glucuronic acid; sulfuric acid esters were not found. All conjugated metabolites were rapidly excreted in the bile but some were also released into the circulation. The enzymatic systems responsible for the metabolism and excretion of benzo(a)pyrene 4,5-oxide remained viable in the isolated perfused liver for at least 60 min. The toxicological significance of the release of polycyclic aromatic hydrocarbon metabolites from the liver into the vascular circulation and the possible significance of UDP:glucuronyltransferase activity in preventing chemically induced carcinogenesis are discussed.