The effect of severe liver disease on ranitidine disposition was evaluated by comparing its kinetics in 5 healthy subjects and 11 patients with alcoholic cirrhosis. Cirrhotic patients had severe liver disease as evidenced by the presence of ascites, hepatic encephalopathy, jaundice, muscle wasting, and low serum albumin, but creatinine clearance did not differ significantly between controls and cirrhosis. Following intravenous administration of ranitidine, systemic clearance was decreased in cirrhosis. These decrease may be associated with changes in renal function, and decrease in hepatic metabolism, usually present in patients with severe hepatic failure. The distribution volume of ranitidine was also decreased in cirrhotics, but the difference between patients and controls was not significant. Biological half-life was significantly longer in cirrhotic patients than volunteers. This difference may be due to decrease in total body clearance found in cirrhotic patients. It is concluded that patients with severe liver cirrhosis could have elevated plasma level of ranitidine and that a reduction of ranitidine dosage is warranted in these patients.