The purpose of the investigation was to study the metabolism of erythropoietin (EPO) in patients with liver disease. Twelve patients with liver cirrhosis and 10 healthy volunteers were studied. The patients were moderately anemic with a hematocrit of 33 vs 42% (medians) in the volunteers. The pharmacokinetic parameters were calculated after an intravenous (i.v.) injection of 100 U/kg of recombinant human EPO. The serum EPO was measured by radioimmunoassay at regular intervals until 48 h. The median terminal elimination half life in the cirrhosis patients was 5.15 h vs 5.37 h in the control subjects. The clearance was 7.78 vs 7.52 ml/min/1.73 m2 (ns). The steady-state volume of distribution was 3.69 vs 3.09 1/1.73 m2 (ns). The estimated endogenous EPO production was significantly higher in liver cirrhosis (486 vs 290 U/d/1.73m2, p < 0.01). The basal serum EPO was significantly higher in the cirrhosis patients (43.5 vs 26.3 U/l, p < 0.01). The hematocrit correlated inversely with the basal serum EPO level in the cirrhosis patients (r = -0.63, p < 0.04). The EPO-clearance was not related to the presence of ascites, esophageal varices, or to abnormal blood chemistry. It was concluded that normal metabolism of EPO was maintained in liver cirrhosis and that the cirrhotic patients had a moderate compensatory increase of EPO production in response to anemia.