The role of circulating endothelin-l, a potent vasoconstricting peptide, in liver cirrhosis is still controversial. It has been postulated that endothelin-l may play a role in the circulatory derangement occurring in cirrhotic subjects, and increased plasma endothelin-l levels have been reported in these patients. In this study we looked for a relationship between the severity of the liver disease according to Child's classification and plasma endothelin-l concentrations in a group of cirrhotic patients compared with a healthy control group. Twenty-two cirrhotic patients and 10 healthy controls, matched for sex and age, were selected for study after informed consent. The etiology of cirrhosis was posthepatitis B in 8 of 22 cases, posthepatitis C in 13 of 22 cases, and alcoholism in I patient. According to Child's classification, 6 patients were in class A, 6 in class B, and 10 in class C. Plasma endothelin-l was measured by a commercial RIA kit (Amersham UK). Mean +/- SD plasma endothelin-l levels were 8.8 +/- 0.9 pg/ml in controls and 9.2 +/- 1.1 pg/ml in all cirrhotic patients (P > 0.05). In each. subgroup of cirrhotics, plasma endothelin-1 was 8.6 +/- 1.2 pg/ml in Child A, 8.9 +/- 1.9 pg/ml in Child B, and 10.6 +/- 1.5 pg/ml in Child C groups, respectively. There were no statistical differences between control subjects and Child A and B cirrhotic patients (P > 0.05). A significant increase in endothelin1 was observed only in the Child C group versus either group A or B (P = 0.004). Our results show that alterations of circulating endothelin-l do not occur in all cirrhotic patients; higher plasma levels than controls are only detectable in patients with more-severe hepatic failure. We do not know whether increased endothelin-l levels are a consequence of hemodynamic disorders occurring in the advanced phase of liver cirrhosis or play a pathogenic role.