Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are examination procedures that have shown that repetitive transcranial magnetic stimulation (rTMS) is biologically active. The aim of the present study was to investigate the patterns of regional cerebral 18F-fluorodeoxyglucose (18F-FDG) uptake and regional 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) uptake simultaneously during a series of therapeutic rTMS at low frequency. Four drug-resistant depressed patients underwent 10 rTMS as an add-on measure over 14 days. One day before and one day after TMS, simultaneous measurements of 18F-FDG, representing regional cerebral metabolic rate (rCMR), and 99mTc-HMPAO, representing regional cerebral blood flow (rCBF), were carried out. A conventional double head SPECT camera with 511 keV collimators was used. Statistically significant simultaneous overall changes of rCBF and rCMR were found in the upper prefrontal regions bilaterally in terms of increased uptake rates and in the left gyrus frontalis inferior in terms of decreased uptake rates of both isotopes compared to controls. Although this method improves our understanding of rTMS mechanism, there are limitations due to the lower resolution provided. Therapeutic rTMS seems to influence distinct, cortical regions affecting rCBF and rCMR.