Pulmonary hypertension is uncommonly associated with portal hypertension. The current approach for the management of pulmonary hypertension involves the use of vasodilators in patients who show vascular responsiveness during an acute challenge. Since the association of portal hypertension with pulmonary hypertension is very seldomly presented, its optimal therapy has not been defined. Moreover, calcium-channel blockers, which are usually used in pulmonary hypertension treatment, may exert a deleterious effect on portal hypertension. Therefore, the search for drugs that may be active under both conditions has important clinical implications. This report presents the case of a patient with portal hypertension-associated pulmonary artery hypertension that was effectively treated with isosorbide-5-mononitrate (Is-5-Mn). The patient had severe portal hypertension (hepatic venous pressure gradient=14.5 mmHg) and pulmonary hypertension (mean pulmonary artery pressure (PAP)=50 mmHg). Acute administration of prostacyclin and nitric oxide elicited a significant reduction in both PAP and pulmonary vascular resistance (PVR), an effect that was also achieved with Is-5-Mn. The patient was treated with 40 mg Is-5-Mn twice daily and a haemodynamic study performed 6 months later showed that the reduction in both PAP and PVR persisted.