In the present study, we investigated the mechanism for the decrease in levels of serum thyroid hormones, especially thyroxine (T₄) , by polychlorinated biphenyls (PCBs) such as Kanechlor-500 (KC500) , 2,2’,4’,5,5’-pentachlorobiphenyl (PentaCB) , and 2,2’,3’,4’,5,6-hexachlorobiphenyl (HexaCB) , and studied species differences among mice, hamsters, rats, and guinea pigs in the PCB effect. Significant decrease in serum total T₄ level by KC500 was observed in all four species. On the other hand, there were differences in the level of decrease of serum total T₄ level by PentaCB and HexaCB. Differences in the level of hepatic methylsulfonyl-PCB metabolites of KC500, PentaCB and HexaCB, which were thought to be associated with the PCB-toxic effects, did not necessarily correlate with the magnitude of decrease in serum total T₄ level. Likewise, the induction of UDP-glucuronosyltransferases (T₄-UDP-GT) toward T₄ by PCB did not necessarily correlate with the decrease in serum T₄ level in the animals used. Further studies on transthyretin (TTR) and serum T₄-transporter suggested that decrease in serum total T₄ level induced by PCB occurred not only by induction of T₄-UDP-GT but also by the alteration of levels of T₄-TTR binding and hepatic T₄-transporter. In addition, species difference in the decrease of serum total T₄ was associated with various PCB-induced total effects, including induction of T₄-UDP-GT, decrease in T₄-TTR binding level, the increase of hepatic thyroid hormone transporter, and other thyroid function correlates.