Objectives: 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 × 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. Conclusion: 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.