The relationships between the changes in the levels of serum total thyroxine (T-4). serum T-4-transthyretin (TTR) complex, and accumulation of T-4 in tissues by 2,2',4,5,5'-pentachlorobiphenyl (PentaCB) were examined using wild-type C57BL/6 (WT) and its TTR-deficient (TTR-null) mice. The constitutive level of serum total T-4 was much higher in WT mice than in TTR-null mice. In WT mice 4 days after a single intraperitoneal injection with PentaCB (112 mg/kg), serum total T-4 level was significantly decreased along with a decrease in serum T-4-TTR complex, and the levels of serum total T-4 in the PentaCB-treated WT mice were almost the same to those in PentaCB-untreated (control) TTR-null mice. In addition, a slight decrease in serum total T-4 by PentaCB treatment was observed in TTR-null mice. Furthermore, clearance of [I-125]T-4 from the serum after [I-125]T-4-administration was promoted by the PentaCB-pretreatment in either strain of mice, especially WT mice. On the other hand, accumulation level of [I-125]T-4 in the liver, but not in extrahepatic tissues, was strikingly enhanced in the PentaCB-pretreated WT and TTR-null mice. Furthermore, in both strains of mice, PentaCB-pretreatment led to significant increases in the steady-state distribution volume of [I-125]T-4 and the concentration ratio of the liver to serum. The present findings demonstrate that PentaCB-mediated decrease in serum T-4 level occurs mainly through increase in accumulation level of T-4 in the liver and further indicate that the increased accumulation of T-4 in the liver of WT mice is primarily dependent on the PentaCB-mediated inhibition of serum T-4-TTR complex formation. (C) 2012 Elsevier Inc. All rights reserved.