Propranolol and molsidomine have both been shown to decrease the hepatic venous pressure gradient in patients with cirrhosis. The present study aimed at assessing the effects of the combination of these two drugs on splanchnic and systemic haemodynamics of cirrhotic patients. Fifteen patients with biopsy proven alcoholic cirrhosis had haemodynamic measurements under basal conditions, 60 min after oral administration of 4 mg molsidomine then 15 min after intravenous administration of 15 mg propranolol. As compared with baseline values, molsidomine was found to decrease mean arterial pressure (-7.9%, (P < 0.01), cardiac output (-7.3%, P < 0.01), pulmonary wedged pressure (-45.8%, (P < 0.05) and hepatic venous pressure gradient (-11.7%, P < 0.01). Propranolol decreased heart rate (-21%, P < 0.01), further decreased cardiac output (-20.6%, (P < 0.01) and hepatic venous pressure gradient (-10.5%, P < 0.01). As a whole, molsidomine plus propranolol decreased mean arterial pressure (-8%, P < 0.01), heart rate (-19%, P < 0.01), cardiac output (-26.5%, P < 0.01) and hepatic venous pressure gradient (-21%, P < 0.01). Pulmonary wedged pressure, liver blood flow and hepatic intrinsic clearance of indocyanine green were not significantly changed by the association of molsidomine and propranolol. We conclude that in patients with cirrhosis, molsidomine and propranolol potentiate their effects on hepatic venous pressure gradient. Such a combination could therefore prove useful in the treatment of portal hypertension.