Furosemide disposition in 7 cirrhotic subjects and 4 age-matched healthy controls was studied to determine the contribution of differences in pharmacokinetics to the decreased responsiveness observed in cirrhotics. Subjects were given 80 mg of furosemide orally and intravenously on separate occasions, and plasma and urine samples were collected and analyzed for furosemide by high performance liquid chromatography. The half-life of furosemide was 74% greater in the cirrhotic subjects, the result of a smaller increase in volume of distribution (30%) and a decrease in total plasma clearance (15%). The change in plasma clearance was due entirely to a change in nonrenal clearance, since renal clearance was very similar in both groups. The fraction of furosemide not bound to plasma proteins increased by 48%. Furosemide bioavailability was the same in cirrhotic subjects and controls. Consistent with other reports, there was considerable intersubject variability in all of the measured and computed parameters. The results show that differences in disposition play little, if any, role in the decreased renal responsiveness to furosemide.