The antianginal activity of trimetazidine was evaluated in a double-blind, multicentric, drug-versus-placebo study. The 32 male patients who entered the study (mean age 59.5 years) were suffering from stable angina pectoris. The stability of angina was tested by two exercise tests performed at the beginning and at the end of a two-week preselection period with placebo. The patients received 3 tablets daily of either trimetazidine (20 mg per tablet) or placebo for one month. At the end of treatment, they underwent a third exercise test. A Mann and Whitney test, used to compare the result of pre- and post-treatment exercise tests, showed a statistically significant improvement with trimetazidine as compared with the placebo for the following parameters: total work went from 4.200 +/- 372 to 5.620 +/- 387 kpm with trimetazidine and from 4.191 +/- 399 to 4.564 +/- 431 kpm with the placebo (P = 0.012); duration of exercise from 10.2 +/- 0.5 to 12.1 +/- 0.5 min with trimetazidine and from 10.2 +/- 0.5 to 10.7 +/- 0.5 min with the placebo (P = 0.016); time to 1 mm ST segment depression from 8.3 +/- 0.6 to 9.8 +/- 0.5 min with trimetazidine and from 8.4 +/- 0.5 to 9 +/- 0.7 min with the placebo (P = 0.034). These results showed that the ischaemic threshold receded with trimetazidine, while the peripheral haemodynamic parameters were not significantly changed, either at rest or during exercise. Thus, trimetazidine does not act through a chronotropic or vasodilator mechanism but through cellular regulation mechanism.