The purpose of this study was to compare HMPAO- and IMZ-SPECT findings in treated and untreated patients with focal epilepsies. We examined 20 patients (untreated 13; treated 7). All patients had a normal CT and/or MRI scan. In all patients both whole-brain activity and regional count density (rcd) were evaluated by SPECT. Furthermore, the specific and non-specific binding of IMZ were calculated for each ROI and the results of both, treated and untreated patients were compared. Our data indicate that the normalized cerebral total binding of IMZ was significantly increased in all regions in the group of treated patients (p < 0.001). In contrast, no difference in the tracer binding was found with HMPAO-SPECT. We conclude that the difference in the IMZ-binding might be due either to exogenous or endogenous factors. In our study IMZ-SPECT had a higher sensitivity and a lower specificity in the detection of decreased rcd in areas with EEG findings that indicate an epileptogenic focus compared with HMPAO-SPECT.