Endothelin is a newly discovered potent vasoconstrictor peptide. To explain the clinical significance of endothelin in patients with chronic liver diseases, we measured the plasma concentration of endothelin in patients with chronic hepatitis (n = 15), cirrhosis with ascites (n = 8) and cirrhosis without ascites (n = 12), and we compared the findings with the plasma concentration of endothelin in normal controls (n = 14). The plasma endothelin concentration was significantly higher in patients with cirrhosis with ascites than in normal controls (8.3 +/- 2.3 pg/ml vs. 3.3 +/- 1.4 pg/ml, mean +/- S.D., p less than 0.001), whereas no significant difference was observed between normal controls and the other groups of patients (cirrhosis without ascites = 5.0 +/- 1.3 pg/ml; chronic hepatitis = 3.8 +/- 1.2 pg/ml). In patients with cirrhosis, the plasma endothelin concentration showed a significant negative correlation with creatinine clearance (r = -0.73, p less than 0.01), but no significant correlation was observed between plasma endothelin concentration and fractional excretion of filtered sodium. Furthermore, plasma endothelin levels were significantly higher in patients with endotoxemia than in those without (10.1 +/- 2.1 pg/ml vs. 4.9 +/- 1.2 pg/ml, p less than 0.001). From these results, elevated plasma endothelin, which has a close relation to endotoxemia, may play a contributory role in kidney dysfunction in patients with cirrhosis.