In the liver, drugs with phenolic groups can be converted to sulfate or glucuronide conjugates and are then transported into bile or back into the bloodstream. The mechanism for transport of drugs and drug conjugates from the hepatocytes into the blood at the sinusoidal side of the cell are not well defined. In the case of carrier-mediated transport of these strongly polar conjugates, saturability of transport and mutual competition between structurally related compounds would be anticipated. This competitive aspect was investigated by using two organic anions, dibromosulfophthalein (DBSP) and harmol sulfate. The latter compound was generated by the hepatocytes from harmol, which was continuously infused into the rat in vivo and in isolated perfused rat livers. In addition we loaded the perfused rat livers with preformed harmol sulfate and studied its efflux rate to the perfusate as influenced by DBSP. In steady state, about 80% of harmol was sulfated and 20% was glucuronidated. Harmol sulfate was mainly excreted in the urine, the glucuronide was equally excreted in urine and bile. DBSP lowered the urinary excretion of harmol sulfate by about 30% which was due to a decrease in plasma concentration. However, renal clearance of harmol sulfate (3.2 +/- 0.2 ml/min) was unchanged. At the same time DBSP doubled the biliary clearance of harmol sulfate (1.0 +/- 0.1 and 2.2 +/- 0.2 ml/min in controls and DBSP studies respectively). DBSP decreased glucuronide excretion both in urine and bile. The increase in biliary output and decrease in urinary excretion of harmol sulfate is explained by competitive interaction between the organic anion DBSP and harmol sulfate at the sinusoidal level. Efflux experiments in single pass perfused isolated livers showed a clear decrease of harmol sulfate transport from liver into plasma by DBSP and provided evidence for such an inhibitory phenomenon (t 1/2 of efflux was 3.58 +/- 0.21 compared with 2.46 +/- 0.07 min for controls). These results indicate that organic anion transport from the hepatocyte into the blood stream is very likely carrier-mediated. A decrease in renal output of drug conjugates therefore may not only be due to a decrease in the conjugation process but also to a lower liver to blood transport rate which at the same time may produce a higher biliary output.