The role of acute pulmonary vasodilator testing in portopulmonary hypertension (PoPH), a current contraindication for orthotopic liver transplantation (OLT), has not been thoroughly elucidated. The purpose of this work was to analyze the results of acute vasodilator testing with inhaled nitric oxide (NO), to compare them with intravenous epoprostenol (PGI 2 ), and to investigate the acute effects of the oral vasodilator isosorbide-5-mononitrate (Is-5-MN), in patients with PoPH. A total of 19 patients with PoPH (male/female ϭ 9/10) were studied. Pulmonary hemodynamic measurements were performed at baseline and during NO inhalation (40 ppm); additionally, 15 patients were tested with PGI 2 (2-12 g/kg/minute) and 8 were tested with Is-5-MN (20-40 mg). Inhaled NO reduced pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) by 5.7% and 11.0%, respectively. PGI 2 elicited greater reductions in PAP (11.8%) and PVR (Ϫ24.0%), and produced a 28% drop in systemic vascular resistance (SVR) and a 17% increase in the cardiac index (CI). Is-5-MN reduced PAP by 25.6% and PVR by 21.5%, without systemic changes. There was good agreement between the response to PGI 2 and Is-5-MN: 6 patients of the whole series (32%) decreased PAP Ͼ20% from baseline, reaching a final value Յ35 mmHg, the current limit for OLT. In conclusion, acute vasodilator testing has a relevant role in PoPH, as it identifies one-third of patients able to reach a more favorable hemodynamic situation, which can be determinant for their management. For vasodilator testing, PGI 2 is more suitable than NO in PoPH. Is-5-MN exerts a selective effect on pulmonary circulation in patients who had already responded to PGI 2 .