The use of angiotensin II antagonists in the treatment of portal hypertension remains controversial. Our aims were to assess the effect of Irbesartan on portal pressure and to evaluate its safety in cirrhotic patients with portal hypertension. Twenty-five cirrhotic patients were treated in a pilot study with Irbesartan 300 mg orally once daily for 60 days. Hemodynamic evaluations and biochemical tests were performed before therapy and after two months of treatment. Three patients (12%) discontinued treatment for symptomatic arterial hypotension (mean arterial pressure -26.% +/- 3.1 versus basal). In the 18 responders, the hepatic venous pressure gradient diminished by a mean of 18.1% +/- 10.5 from baseline (p = 0.02); the gradient decreased by 20% or more in only 5 patients (23%). The mean arterial pressure decreased significantly during therapy (92 +/- 7 vs 109 +/- 25 mm Hg, P < 0.001). In conclusions, Irbesartan induced a marginal reduction in portal pressure and its safety was limited by the pronounced effects on arterial pressure.