The in vitro metabolism of 4-chlorobiphenyl, a model polychlorinated biphenyl (PCB) substrate, proceeds via an arene oxide intermediate to give the observed in vivo hydroxylated metabolites. The rabbit liver microsomal fraction mediates binding between the PCB and the endogenous microsomal protein and RNA and the major part of the PCB was bound to the light 3S[Svedberg units]-10S RNA fraction. The lower chlorinated 4-chlorobiphenyl isomer was highly mutagenic to the Salmonella typhimurium strain TA1538 (sensitive to frameshift mutagens) whereas higher chlorinated PCB were only weakly mutagenic. [Carcinogenicity of PCB, industrial compounds and pollutants, is discussed.].