Trimetazidine (TMZ) has recently been shown to improve anginal symptoms without altering haemodynamic variables. A randomized, double-blind, placebo-controlled study was conducted in 20 patients to study the effects of TMZ on the severity of myocardial ischaemia during PTCA of the left anterior descending coronary artery. Five minutes after a first successful dilatation (D0), a control balloon inflation (D1) was performed until onset of ischaemic signs on both the intracoronary (i.c.) and precordial ECG. Two minutes later, patients received either TMZ 6 mg or placebo i.c. Another inflation (D2) was performed 5 min after D1. No differences were found between the two groups regarding responses in heart rate, systemic and i.c. pressures during the study. TMZ decreased the maximum ST-segment shift at D2 compared with D1 (0.8 +/- 0.1 vs 1.4 +/- 0.3 mV, P = 0.023) and delayed its onset (46 +/- 4 vs 36 +/- 5 s, P = 0.024). TMZ also decreased maximum T-wave changes (1.06 +/- 0.24 vs 2.19 +/- 0.3 mV, P = 0.001), and significantly reduced the area under the curve (mv s-1) of the i.c. ST-segment and T-wave changes during balloon inflation (P = 0.042 and P = 0.009 respectively). The placebo had no effect on these parameters. These results support the hypothesis that trimetazidine has a direct anti-ischaemic effect on human myocardial cells.