Among several brain radiopharmaceuticals for SPECT imaging, 99mTc complexes of HMPAO and ECD are the most widely used. They are considered to be equal in their capacity to reflect regional cerebral blood flow; but discrepancies between HMPAO and ECD brain uptake have been reported in stroke patients. This paper reports our observations regarding discrepancies between HMPAO and ECD SPECT in 14 of 23 patients with suspected brain tumors or presumed metabolic cerebral abnormalities. We obtained similar conflicting results, namely focal HMPAO hyperactivities and isoactive ECD SPECT. The majority of these discrepancies were found in patients with brain tumors (10 of 13 patients), while only 4 of the 10 remaining patients with nontumoral process showed similar discrepant results. The physiopathology behind these observations is discussed here, and it is likely to be related to the specific response to cellular metabolic disorders rather than to perfusion disturbances.