The aim of this study is to investigate regional cerebral blood flow (rCBF) in patients with syncope. We compared brain single photon emission computed tomography (SPECT) images of neurally mediated syncope patients with those of age/sex matched healthy volunteers. (99m)Tc-ethylcysteinate dimer (ECD) brain SPECT was performed in 35 patients (M/F = 17/18, mean 36.6 years) with syncope during the asymptomatic period, and in 35 healthy volunteers. For statistical parametric mapping (SPM) analysis, all SPECT images were spatially normalized to the standard SPECT template and then smoothed using a 14-mm full width at half maximum Gaussian kernel. The mean duration of syncope history was 4.9 years and the mean number of syncope episodes was 6.3. In all patients, syncope or presyncope episodes occurred during head-up tilt tests, and all were the vasodepressive type. SPM analysis of brain SPECT images showed significantly decreased rCBF in the right anterior insular cortex, left parahippocampal gyrus, bilateral fusiform gyri, bilateral middle and inferior temporal gyri, left lingual gyrus, bilateral precuneus and bilateral posterior lobes of the cerebellum in syncope patients at a false discovery rate corrected p < 0.05. There were no brain regions that showed increased rCBF in syncope patients. Furthermore, we found a negative correlation between the total number of syncopal episodes and the rCBF of the right prefrontal cortex, and between the duration of syncope history and the rCBF of the right cingulate gyrus at uncorrected p < 0.001. Decreases of rCBF in multiple brain regions may be responsible for autonomic dysregulation and improper processing of emotional stress in neurally mediated syncope patients, and frequent syncope episodes may lead to frontal dysfunction.