To assess the role of the liver in the elimination of furosemide, the disposition kinetics of the diuretic after intravenous administration were studied in dogs with total devascularization of the liver and sham-operated animals. Functional hepatectomy caused no significant changes in either the renal or the nonrenal clearances of furosemide; renal = 124.2 +/- 27.1 (mean +/- SE) and 106.6 +/- 17.5 ml/min and nonrenal = 148.2 +/- 11.4 and 112.6 +/- 21.0 ml/min in sham-operated and hepatectomized dogs, respectively. Devascularization of the liver had no effect on the plasma binding of furosemide which was 90.0% in the sham-operated and 88.2% in the hepatectomized animals. The steady-state volume of distribution of furosemide was relatively small, 0.70 +/- 0.09 liters/kg in control dogs and hepatectomy resulted in a reduction in this volume (0.58 +/- 0.09 liters/kg). This indicates that the liver is a significant organ for distribution of furosemide in the dog. Urinary recoveries of parent drug (43.2% of the dose in sham-operated dogs ad 49.1% in hepatectomized animals) and of its glucuronide (4.3% in sham-operated and 5.5% in hepatectomized dogs) were not influenced by hepatic devascularization. These findings demonstrate that, although nonrenal clearance accounts for about 50% of the elimination of furosemide, the liver does not play a significant role in this process in the dog.