Portal hypertension and its complications (variceal bleeding, encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome) are the main cause of death and liver transplantation in patients with cirrhosis. Diminishing portal hypertension by drugs (beta-blockers) is associated with a protection in the development of complications from portal hypertension. For this reason it is important to investigate and develop drugs that can reduce the portal pressure in liver cirrhosis. Tetrahydrobiopterin has been shown to decrease portal pressure in animal models of cirrhosis by improving intrahepatic resistance and by increasing nitric oxide bioavailability (eNOS co-factor). These effects were not associated to deleterious effects on systemic hemodynamics.