Changes in the mode of drug excretion in obstructive jaundice (OJ) were investigated in rats with experimentally induced OJ using a non-metabolized, highly-biliary-excreted antibiotic, cefpiramide (CPM). In OJ rats, biliary excretion of the drug was markedly diminished, while the urinary excretion was increased. The change in the mode of CPM excretion was examined in detail. It seems that the biliary excretion of CPM was decreased owing to the diminished biliary clearance in OJ rats. On the other hand, CPM binding to plasma proteins was decreased in the disease state. This change in the protein binding would be due to both the decreased albumin concentration and the accumulation of binding inhibitors in the plasma of diseased rats, and the decreased protein binding would be related not only to the increase in the volume of distribution but also to the increase in the renal clearance.