This randomized double-blind controlled study analyzed the hemodynamic effects of penbutolol, a new levo-rotatory betablocker, using radionuclide angiography. Twenty cirrhotics with esophageal varices were randomized: 10 received 40 mg/day of penbutolol orally and the others a placebo. Angioscintigraphy was performed before and after an 8-day treatment period. Three cases in the penbutolol group were lost due to software damage, hence the data of 17 patients were analyzed. The two groups were similar for age, sex, etiology of cirrhosis and hepatic function. The index of portal perfusion decreased significantly (-29%; p = 0.018), and the hepatic artery index increased significantly (+23%; p = 0.018), whereas no changes were observed after placebo. The heart rate decreased significantly after penbutolol (-9%; p = 0.021); while neither penbutolol nor placebo modified the ejection fraction. In conclusion, penbutolol decreased portal perfusion index (the compensatory increase of hepatic artery index confirmed this change) without significant modification of total hepatic blood flow and systemic hemodynamics. Angioscintigraphy is reasonably accurate, reproducible, safe and can be considered suitable for routine use in the assessment of liver hemodynamics.