Previous experimental studies have suggested that the paracrine endothelin system may participate in the regulation of hepatic hemodynamics in cirrhosis. The present study assesses the relationship between increased portal pressure and preproET-1, ET(A) receptor and ET(B) receptor gene expression in human cirrhosis. PreproET-1, ET(A) receptor and ET(B) receptor mRNA abundance was estimated by quantitative PCR in human hepatic tissue from subjects with normal liver and in cirrhotic patients in whom a hepatic hemodynamic study was performed. The expression of the three transcripts was significantly higher in liver samples of cirrhotic patients than in those obtained from subjects without any histological alteration. Moreover, while no significant correlation was found between preproET-1 mRNA abundance and portal pressure, there was a highly significant direct relationship between ET(A) and ET(B) receptor gene expression and portal pressure in cirrhotic patients. These results indicate that the liver paracrine endothelin system is overactivated in human cirrhosis and that a direct relationship exists between endothelin receptor mRNA abundance and the degree of portal hypertension in these patients.