Recent evidence suggests that myocardial ischemia may occur in patients with neurally mediated syncope and normal coronary angiograms. This study was conducted to evaluate if coronary microvascular function is impaired in such patients. Coronary hemodynamic studies and head-up tilt table tests (HUTs) were performed on 30 consecutive patients with normal coronary angiograms and recurrent syncope. Another ten subjects with atypical chest pain and no evidence of myocardial ischemia or syncope served as a control. Great cardiac vein flow (GCVF) and coronary sinus flow (CSF) were measured by the thermodilution method at baseline and after dipyridamole infusion (0.56 mg/kg i.v. for 4 minutes). Coronary flow reserve (CFR), derived from CSF and GCVF, was significantly lower in the 15 patients with positive HUT than in the other 15 patients with negative HUT (1.75 +/- 0.48 vs 2.64 +/- 0.8, P < 0.01 and 2.29 +/- 0.45 vs 3.07 +/- 0.63, P < 0.01, respectively). Ischemic-like ECG was noted during treadmill exercise test in 40% of the former and in 7% of the latter group (P = 0.01). There was no significant difference in CFR between patients with negative HUT and control subjects. Coronary microvascular function was impaired in syncopal patients with positive HUT and relatively preserved in those with negative HUT, suggesting the possible linkage between coronary microvascular dysfunction and the development of neurally mediated syncope.