BACKGROUND: There is growing evidence that high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex is effective in the treatment of depression. Brain imaging studies have shown that rTMS alters regional brain activity with improvement of depression. However, a predictor of treatment response to rTMS has not yet been identified. OBJECTIVE: The aim of this study was to estimate regional cerebral blood flow in the frontal regions and investigate the correlation with treatment response to high-frequency rTMS over the left dorsolateral prefrontal cortex in depression. METHODS: Twenty-four patients with depression received high-frequency rTMS over the left dorsolateral prefrontal cortex and were assessed with the Hamilton Depression Rating Scale. Brain scans were acquired before rTMS using (99m)Tc-ethyl cysteinate dimer single photon emission computed tomography (SPECT), and cerebral blood flow in 16 brain regions was estimated using a fully automated region of interest (ROI) analysis software. Two principal components were extracted from cerebral blood flow in 16 brain regions by factor analysis with maximum likelihood method and Promax rotation with Kaiser normalization. RESULTS: Sixteen brain regions were divided into two groups: dorsolateral prefrontal cortex (superior frontal, medial frontal, middle frontal, and inferior frontal regions); ventromedial prefrontal cortex (anterior cingulate, subcallosal, orbital, and rectal regions). Treatment response to rTMS was correlated with cerebral blood flow ratio of the dorsolateral prefrontal cortex to the ventromedial prefrontal cortex (DLPFC/VMPFC CBF ratio, r = -0.60, P = 0.002). CONCLUSIONS: The findings of this study suggest that depressed patients with a lower DLPFC/VMPFC CBF ratio may show a better response to high-frequency rTMS over the left dorsolateral prefrontal cortex.