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Sodium dehydrocholate administration significantly impaired bromosulfophthalein (BSP) clearance in six normal volunteers, despite its choleretic effect. In order to determine whether the impairment is at the stage of excretion of BSP from the liver cell into the bile, patients with Dubin-Johnson syndrome were studied. In all six Dubin-Johnson patients, sodium dehydrocholate administration significantly decreased BSP clearance. Since serum bile acid levels are normal in Dubin-Johnson patients, presumably due to a final secretory pathway into the bile distinct from that of BSP and other organic anions, the interaction between BSP and bile acids cannot take place at the stage of excretion into the bile. Based on a previous study and our results, the interaction between BSP and bile salts seems to occur at the site of transport within the liver cell. This mechanism of inhibition may be responsible for the increased serum BSP retention during chemotherapy.