Previous studies have suggested that angiotensin-converting enzyme inhibitors (ACEI) promote collateral circulation in ischemic limbs of rabbits. The present study was designed to determine the association between treatment with ACEI and the development of coronary collateral circulation, as assessed by the Rentrop Score, in patients with coronary artery disease (CAD) in a case - control study. Subjects included 456 patients with angina who underwent coronary angiography. Those who had one (1-V), two (2-V) or three (3-V) significantly stenosed vessels, and who received only ACEI without any other anti-hypertensive medication were defined as cases (n=33), and age, sex and body mass index-matched subjects (n=56) were selected as controls. Among 1-V patients, but not 2-V or 3-V patients, the cases included a higher percentage of patients with Rentrop Score of at least 1 than the controls, suggesting that ACEI was associated with coronary collateral circulation. Patients with 1-V disease who were treated with ACEI were most likely [odds ratio (confidence interval): 6.1 (1.4-30.1)] to develop collateral circulation, as assessed by a multiple logistic regression analysis. Therefore, treatment with ACEI was associated with the development of collateral circulation in patients with CAD, suggesting that such an action is associated with bradykinin production by ACEI.