OBJECTIVE Although the pathophysiology of syndrome X (angina pectoris, positive ECG test findings and normal coronary arteriogram) is unclear, it is generally accepted that intracellular metabolic changes resulting from abnormal constriction of prearteriolar vessels due to endothelium-dependent vasodilation abnormalities may play a role in the pathogenesis. We established the effect of long-term treatment with cilazapril, an angiotensin-converting enzyme inhibitor, which prevents the effect of angiotensin II in the tonic control of vascular resistance. METHODS 18 patients (15 women and 3 men, mean age 43.2 +/- 4.6 years) with syndrome X were included in this study. A randomized double-blind crossover placebo-controlled trial was done. After a 1-week washout period, patients received either cilazapril 2 x 2.5 mg or placebo for 3 weeks, followed by 3 weeks of the other therapy. At the end of two periods, an exercise ECG test (modified Bruce protocol) was employed. RESULTS The magnitude of ST segment depression was significantly decreased during treatment with cilazapril compared with placebo. On the other hand, total exercise time and time to 1 mm ST segment depression were significantly prolonged by cilazapril. However, rate pressure products were not significantly different at peak exercise at or at 1 mm of ST segment depression during both therapies. CONCLUSIONS Cilazapril exerted a beneficial therapeutic effect in cases with syndrome X. The possible mechanism of this effect may be a modulation of coronary tone at the microcirculation level.