The purpose of this study was to determine changes in regional cerebral blood flow (rCBF) associated with premenstrual syndrome (PMS). Regional CBF was examined using single photon emission computed tomography (SPECT) in seven women who sought treatment for PMS and seven control subjects. Confirmation of PMS was based on the Daily Symptom Report (DSR) of 17 common symptoms associated with PMS. A first SPECT scan was performed near the peak of premenstrual symptoms based on DSR reports from the two previous cycles. A second scan was performed in the postmenstrual period. Prior to scanning each subject had a Hamilton Depression Rating Scale (Ham-D) obtained. Regions of interest were drawn on the images to generate mean counts per pixel, and normalized to the cerebellum. Activity in the frontal, temporal and parieto-occipitai cortices, and the thalami and basal ganglia, were compared between the two scans. Correlations between activity in each region of interest and Ham-D values were also determined. There were marked decreases in rCBF in the temporal lobes on the premenstrual scan compared to the postmenstrual scan in PMS patients. Significant correlations were observed between the change in rCBF in the right and left temporal lobes and the changes in Ham-D scores (r = 0.91, p < 0.01 and r = 0.86, p = 0.01 respectively). No rCBF changes were observed in controls. We conclude that SPECT imaging demonstrates modest decreases in rCBF in the temporal lobes that correlate with the level of depression in subjects with PMS.