The effect of various primary and secondary bile acids on the rates of synthesis of all major bile acids was studied in the live rat with an extracorporal bile duct. Bile acid synthesis was determined using HPLC based on mass or by isotope dilution. Derepressed rates of bile acid synthesis (30-54 h) were inhibited by an infusion of taurocholic acid only at a supraphysiological dose of 500 mumol/kg per h, but not at 300 mumol/kg per h, which approximates the initial bile acid secretion (250 mumol/kg per h). When administered together with taurocholic acid (200 mumol/kg per h) only a high dose of taurochenodeoxycholic acid (100 mumol/kg per h) decreased taurocholic but not tauromuricholic or taurochenodeoxycholic acid synthesis. The only bile acid suppressing taurocholic acid (36-71%) and taurochenodeoxycholic acid (up to 33%) formation at an infusion rate close to the normal portal flux was deoxy- or taurodeoxycholic acid at 15-50 mumol/kg per h. It may be concluded that deoxycholic acid and possibly other secondary bile acids are much more potent inhibitors than primary bile acids.