The effects of flow rate and dl-propranolol pretreatment on the hepatic clearance of lidocaine were studied in the perfused rat liver. Livers were perfused in situ with Krebs' bicarbonate buffer (pH 7.4) containing 35 muM of nonlabeled lidocaine and trace amounts of 14C-labeled lidocaine for up to 60 min at 14 or 7 ml/min. Lidocaine was rapidly eliminated from the perfusate at 14 ml/min but was at slower rate at 7 ml/min. Pretreatment of the livers with various concentrations of dl-propranolol resulted in a marked reduction in hepatic clearance of lidocaine. Metabolic profile also indicated that hepatic degradation of lidocaine was also significantly inhibited in the dl-propranolol-pretreated livers. Results obtained from the present study and those obtained previously from isolated rat hepatocytes indicate that the observed reduction of hepatic clearance and metabolism of lidocaine by dl-propranolol pretreatment may be the result of binding displacement at the hepatic site.