The influence of the bile salts taurocholate and dehydrocholate on the hepatic transport of two quaternary ammonium compounds, D-tubocurarine (dTc) and N4 -acetylprocainamide ethobromide (APAEB) was investigated in rats. The biliary excretion of APAEB and dTc in vivo was not enhanced by 106 mumoles/h of taurocholate or dehydrocholate. Infusion of 268 mumoles/h dehydrocholate caused an inhibition of the plasma disappearance and hepatic transport of dTc. This inhibition, which presumably occurred at the hepatic uptake level, was also observed in isolated perfused rat liver experiments. In animals with an intact renal function, the high dose of dehydrocholate caused a decreased biliary excretion and an increased renal excretion of dTc. The observed concentration gradients, plasma/liver cytosol and bile/liver cytosol 20 min after injection of both drugs were 1.6 and 23 for APAEB and 2.2 and 190 for dTc. These concentration ratios were based on free drug concentrations; corrections were made for plasma protein binding, intracellular binding and bilary micelle binding. No substantial binding of both compounds to ligandin and Z proteins was found. From the amount in the liver 20 min after injection of both drugs 70% of APAEB and 90% of dTc was bound to cellular particles. The rate limiting step in hepatic transport of APAEB from plasma into bile was concluded to be the hepatic uptake, which may explain the lack of effect of bile salt induced choleresis on its biliary excretion.