We conducted a randomized controlled hemodynamic study to evaluate the effect of placebo and 20 mg isosorbide-5-mononitrate, a long-acting organic nitrate, in 19 patients with HBsAg-positive cirrhosis by the simultaneous measurement of portal venous pressure and wedged hepatic venous pressure. Baseline values for the two groups were similar. One hour after oral administration of 20 mg isosorbide-5-mononitrate in 10 patients, mean arterial pressure, mean pulmonary arterial pressure and pulmonary capillary wedge pressure significantly decreased from 92 ± 13 (mean ± S.D.) to 82 ± 14 mmHg, from 12.9 ± 4.5 to 9.3 ± 2.4 mmHg and from 6.9 ± 3.4 to 4.3 ± 1.8 mmHg, respectively. However, both portal venous pressure gradient (from 18.1 ± 3.6 to 17.5 ± 3.0 mmHg) and hepatic venous pressure gradient (from 17.8 ± 5.2 to 16.6 ± 5.3 mmHg) remained unchanged during the study. In six patients who received 20 mg isosorbide-5-mononitrate twice daily for 7 days, hepatic venous pressure gradient remained unaltered as compared to basal and 1-hr values. There was no significant change in cardiac index, heart rate or systemic vascular resistance in either immediate (1-hr) or delayed (7-day) studies. Three patients (30%) developed mild headache or dizziness and two patients (20%) demonstrated systolic hypotension (<80 mmHg) during the immediate study. This study shows that isosorbide-5-mononitrate appears to have no effect in treating portal hypertension in patients with HBsAg-positive cirrhosis. In addition, the isosorbide-5-mononitrate may affect the systemic circulation more than the portal circulation.