Inview of the favourable results of the short-term therapy of acute myocardial infarction (AMI) with glyceryl-trinitrate (GTN) infusion, we undertook a randomized study to test the hypothesis whether the administration of a single dose of isosorbide 5-mononitrate (IS 5-MN) given orally would have the same favourable haemodynamic effect as observed with GTN infusion. For this purpose we evaluated the haemodynamic effects of IS 5-MN compared to isosorbide dinitrate (ISDN), observed in the same group of patients. 10 patients (8 males, 2 females) aged 50-76 years (mean 63) with AMI (7 anterior, 3 inferior) admitted to the coronary care unit within 48 h from onset of symptoms were entered into this single-blind randomized study; at the time of study entry, 8 patients were in Killip class I, and 2 patients in Killip class II. All drugs with haemodynamic effects were withdrawn 12 h before the study started. Both the haemodynamic profile and the clinical status were stable in all patients. Haemodynamic parameters were recorded with a Swan-Ganz thermodilution catheter, cardiac output was measured by the thermodilution method, and the left ventricular ejection time was calculated according to the Weissler method. The echo left ventricular end-diastolic diameter was measured by evaluation of the M-mode echocardiographic recording. The haemodynamic parameters were measured or calculated in basal condition (-30 min, -10 min, control, as well as +30 min and 1, 2, 3, 4, and 5 h after the administration of the drug (IS 5-MN or ISDN 20 mg orally). IS 5-MN treatment results in no significant change of heart rate but in significant decrease of blood pressure (systolic/diastolic), LVED pressure, right atrial pressure and cardiac index. Furthermore, IS 5-MN induced a significant fall of ventricular stroke work index, tension time index and pressure rate product, considered determinant for myocardial oxygen consumption. In the majority of cases the drug exerts its maximum effect within 1 h, lasting for at least 4-5 h. After administration of ISDN, the same patients showed similar but less stable haemodynamic changes (n.s.). In conclusion, it can be expected that 20 mg of IS 5-MN, given orally to patients with AMI, improve haemodynamics for at least 4–5 h.