Polychlorinated biphenyls (PCBs) are widely spread environmental contaminants consisting of chemical mixtures containing many of the 209 possible congeners. The potential immunomodulatory properties of PCBs have been the subject of extensive experimental investigations. The available evidence indicates that the immune system is a target for PCBs and is perhaps one of the most sensitive indicators for adverse PCB-induced health effects. Recent advances regarding the mechanism of PCB-induced immunotoxicity point to their dependency on the presence of the aromatic hydrocarbon receptor and their ability to bind to this receptor as the venue for their toxicological activity. Their binding affinity depends on the degree of chlorination of the biphenyl structure and the position of the chlorine atoms. Such advances have contributed significantly to the determination of the relative immunotoxic potential of PCB mixtures and to the calculation of TEFs for several of the PCB congeners. Such information is critical for evaluating the potential risk PCBs pose to human health. To fully exploit the potential contribution immunotoxicology can make to risk assessment, it is important that the data base on mechanism(s) of PCB-induced immunotoxicity and the potential agonistic/antagonistic properties of PCBs be expanded considerably.