Because 99mTc-HMPAO and 99mTc-ECD are both used for SPECT imaging of cerebral blood flow, the question arises whether there are any differences in their respective regional cerebral distribution. For that purpose, visual and semiquantitative comparisons between 99mTc-HMPAO and 99mTc-ECD studies were performed. METHODS Seventeen patients (4 women; 13 men; age 45-89 yr; mean age 71 yr) with various neurological diseases, except acute/subacute stroke, were investigated twice with 99mTc-HMPAO and 99mTc-ECD using a triple-headed rotating SPECT camera. After image reorientation, the two studies were evaluated visually. Seventy regions of interest (ROIs) were drawn manually and the same set of ROIs was applied in both studies. Regional indices (RI) normalized to individual brain values were calculated and first compared between two random patient groups. Second, for all patients, RI for 70 and later for 27 regions (gained after summing values of corresponding regions in different brain slices) were compared by using a paired Student's t-test applying Bonferroni's correction. RESULTS Visual evaluation demonstrated relatively high 99mTc-ECD uptake in occipital and comparatively low uptake in mediotemporal regions. Calculation of RI revealed significantly higher values in the right cerebellum, brainstem, mediotemporal regions, right basal ganglia and the thalamus in the 99mTc-HMPAO SPECT studies and higher values in the occipital, supratemporal/inferior parietal and parietal cortex in the 99mTc-ECD SPECT studies, respectively. CONCLUSIONS Significant differences in regional tracer distribution between 99mTc-HMPAO and 99mTc-ECD could be detected, probably caused by different tracer kinetics. The results indicate that direct comparisons of studies performed with 99mTc-HMPAO and 99mTc-ECD are not possible and the use of either tracer can be favorable in different clinical questions.