We studied 14 patients, 9 males and 5 females, with an average age of 53.6 ± 9.2 years, having been suffering from effort angina for over 6 months, with positive ergometer test for angina and ST-segment depression > 1 mm. All the patients performed a washout period of 7 days at the end of which, before and after acute administration (90 min) of isosorbide 5-mononitrate or placebo some echocardiographic parameters were controlled according to a double-blind, randomized, crossover design. Moreover, after 2 months of open treatment with isosorbide 5-mononitrate (20 mg three times daily), echocardiographic parameters were investigated again. Continuous ECG monitoring (24 h) was performed after the washout period and after 2 months of treatment. After acute administration of isosorbide 5-mononitrate, we observed a reduction in pre- and afterload, whereas after 2 months of treatment the reduction in preload seems to play a more important role. Together with other mechanisms these haemodynamic changes are responsible for the substantial diminution of myocardial oxygen consumption, and consequently for the reduction of transient ischaemic episodes, both symptomatic and asymptomatic with heart rate increase. These results suggest that isosorbide 5-mononitrate exhibits a definite nitrate-typical vascular activity that is evident both after single administration and after 2 months of treatment.