Background The purpose of this study was to assess the morphological changes and physiological function of coronary arteries in patients presenting with chest pain but having normal coronary angiograms, using intravascular ultrasound imaging (IVUS) and intracoronary Doppler (lCD) flow measurements, in order to elucidate the mechanism of syndrome X.Methods A total of 126 patients [67 males, 59 females, mean age (53.1±13.0) years ] who experienced chest pain but had normal coronary angiograms were included in this study, lCD flow measurements of the left anterior descending coronary artery (LAD) were performed using a Cardiometrics FloMap Ⅱ system. Coronary flow velocity reserve (CFVR) was defined as the ratio of the average peak velocity during hyperemia to that at baseline, induced by an intracoronary bolus injection of 18 μg adenosine. A 3.2F or 2. 9F 30 MHz mechanical rotating ultrasound catheter (CVIS,Boston Scientific) or a 3. OF 20MHz electronic ultrasound catheter (Endosonics) was used for IVUS.Results The mean CFVR value of the LAD was 2.71 ± 0. 74. Reduction of CFVR (＜3.0) was found in 82 of 126 (65.1%) patients. IVUS images of the LAD were available for 109 patients.Plaque formation was detected in 76/109 (69.7%) patients. Based on the presence or absence of plaque formation as well as the reduction or non-reduction of CFVR, patients were divided into four groups: Group I (n =10), normal IVUS findings and normal CFVR; Group Ⅱ (n=23), normal IVUS findings with reduction in CFVR; Group Ⅲ (n =29), IVUS evidence of plaque formation but normal CFVR; and Group IV (n =47), IVUS evidence of plaque formation with reduction in CFVR.Conclusion This study shows the important clinical value of a combination of IVUS and lCD in diagnosing patients with angiographically normal coronary arteries. Only 10% of patients studied (Group I) were found to be truly free of coronary disease, while 20% of patients (Group Ⅱ) would be diagnosed as suffering from syndrome X.