Isosorbide 5-mononitrate (5MI) is a preferential venous dilator that has been shown to decrease portal pressure in acute and long-term haemodynamic studies, and this is not associated with adverse effects on hepatic perfusion. The aim of this trial was to investigate the efficacy and safety of 5MI in the prevention of upper gastrointestinal bleeding in cirrhotic patients. Forty two cirrhotic patients with F2 or F3 esophageal varices showing "red signs" and who had never bled were included and randomly y assigned to receive either 5MI (group I,n23) or placebo (group P,n19). Patients with hepatocarcinomas or complications potentially lethal in the short-term or who were being given drugs such as steroids or interferon were excluded. The end points of the study were bleeding and death. There were no significant differences between the groups in the basal clinical and laboratory data. The mean +/- SD follow-up time was 49 +/- 36 and 43 +/- 25 weeks in the groups I and P, respectively. The percentage of patients free of bleeding 61 weeks after inclusion in the study was 62.4% in the group I and 46.3% in the group P (NS). The percentage of patients surviving 85 weeks after inclusion in the study was 81.2% in the group I and 39.8% in the group P (NS). Treatment did not have to be stopped in any patient of both groups because of side effects. In conclusion, 5MI is a safe drug for the chronic management of portal hypertension, that showed a trend to reduce the risk of bleeding and death in cirrhosis with large esophageal varices.(ABSTRACT TRUNCATED AT 250 WORDS)