The effect of acute renal failure (ARF) on the hepatic uptake and metabolism of propranolol was investigated in relation to the hepatic clearance of the drug. ARF was induced by the subcutaneous injection of uranyl nitrate to rats. The uptake rate of propranolol in the isolated perfused liver was determined by the multiple-indicator dilution method and was found to decrease from 43.6 +/- 2.0 min-1 (mean +/- S.E.) in control to 29.4 +/- 1.7 min-1 in ARF (P less than 0.001). The recovery fraction of propranolol in effluent venous blood increased about twofold in ARF compared to control (P less than 0.05). The metabolic activity for propranolol was examined using the hepatic microsomal fraction prepared from control and ARF rats. There was no significant difference in the kinetics of oxidative metabolism of propranolol between two groups. These results suggest that the previously reported decrease in the hepatic clearance of propranolol in ARF is due to decreased hepatic uptake of the drug from the blood into the liver cells.