Background An impaired coronary flow reserve in syndrome X has been demonstrated by many studies.Recently, however, a normal coronary flow reserve in response to papaverine was reported, but the number of patients in these studies was small. The aim of this study was to investigate whether coronary flow reserve in response to intracoronary papaverine is really impaired in syndrome X.Methods and Results We investigated 53 syndrome X patients (typical angina, a positive exercise test, and completely normal coronary arteries on angiography) and 26 heart transplant patients with normal coronary arteries (control group).All antianginal medications were stopped 48 hours before the study. A 3.6F intracoronary Doppler catheter was positioned in the proximal left anterior descending coronary artery and was connected to a Millar velocimeter. The coronary blood flow velocity at rest and in response to a hyperemic dose of papaverine was measured. Coronary flow reserve was defined as the ratio of hyperemic coronary blood flow velocity in response to papaverine and resting coronary blood flow velocity. The coronary flow reserve (mean+-SD) in the syndrome X group was 2.72+-1.39. The coronary flow reserve in the control group was significantly higher at 5.22+-1.26 (P<.01). In both groups there was no significant difference in the heart rate or the mean arterial pressure during the study.Conclusions Our study shows that coronary flow reserve in response to intracoronary papaverine is impaired in syndrome X patients.(Circulation. 1994;89:1998-2004.)