A single intraperitoneal injection (50 mg/kg) of 3,3',4,4'-tetrachlorobiphenyl (CB77), a 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-type polychlorinated biphenyl, led to significant decreases in the levels of serum total thyroxine (T4) and free T4 without increase in the level of serum thyroid-stimulating hormone at 7 d later in both TCDD-sensitive C57BL/6 and TCDD-resistant DBA/2 mice. When [(125)I]T4 was injected into the mice 7 d after treatment with CB77, the levels of biliary [(125)I]T4 and [(125)I]T4-glucuronide increased 90 to 120 min post injection in C57BL/6 mice, but not in DBA/2 mice, compared with levels in the corresponding control mice. In contrast, in both strains of mice, the CB77-pretreatment led to similar changes in the levels of the [(125)I]T4 bound to the serum transthyretin, albumin, and thyroxine-binding globulin. Consequently, treatment with CB77 promoted the clearance of [(125)I]T4 from the serum and further raised the steady-state volumes of distribution of [(125)I]T4, the concentration ratio (Kp value) of the liver to the serum, and the distribution of [(125)I]T4 in the liver in both strains of mice. The present findings indicate that in mice, the CB77-mediated decrease in the serum T4 level occurs through enhanced accumulation of hepatic T4 rather than through increased activity of hepatic thyroxine-uridine 5'-diphosphate-glucuronosyltransferase(s).