The ileal Na+/bile acid cotransporter (IBAT) maintains the reabsorption of bile acids from the intestine in the enterohepatic circulation of bile acids. In the present study, we showed that S-8921 could dose-dependently inhibit the uptake of [3H] taurocholate in the COS7 cell line which constitutively expresses hamster IBAT. The IC50 value of S-8921 against 60 microM of [3H] taurocholate uptake was 66 +/- 8 microM and kinetic analysis revealed that the inhibition by 100 microM of S-8921 was a mixture of competitive and non-competitive types. In vivo administration of S-8921 by its incorporation into diet (0.001-0.1%) caused dose-dependent decrease of serum cholesterol concentrations accompanied by increased fecal excretion of bile acids in hamsters which were not loaded with cholesterol and bile acid. These data suggest that the inhibition of IBAT could decrease serum cholesterol in the non-cholesterol and -bile acid loaded normal condition.