Measurements of brain blood flow has evolved over the past 50 years, and during the latter half of that time radionuclide techniques have been used to study this important function. Using Xenon 133 and scintillation multiprobe systems, several teams of investigators measured regional cerebral blood flow (rCBF), and noted that under many circumstances it could be equated with local brain physiological activity. The dementias were investigated using the scintillation multiprobe method, and posterior flow deficits were described in patients who were thought to have Alzheimer's disease. The multiprobe technique gave way first to planar, and then tomographic imaging, with initial favorable results achieved by positron emission tomography (PET). Soon investigators learned to measure rCBF with single-photon emission computed tomography (SPECT) using high-sensitivity systems and 133Xe as a tracer, or high-resolution systems with 123I-iodoamphetamine (IMP), and later, 99mTc-HMPAO. Three-dimensional tomographic imaging shows to advantage the flow patterns that characterize Alzheimer's disease, with rCBF reductions in temporal, parietal, and sometimes frontal areas, as opposed to randomly distributed deficits in multiinfarct dementia, reduced frontal flow in entities such as Pick's disease, and others. Herein we will review our own experience with high-sensitivity rCBF SPECT in 119 patients with dementia, and with high-resolution SPECT, using a new, three-camera scanner and 99mTc-HMPAO in an additional 39 patients. SPECT rCBF study of patients with dementia and Alzheimer's disease, will aid in separating patients with untreatable Alzheimer's from those patients who may have treatable causes of dementia, and will be useful in evaluating experimental drugs for the treatment of Alzheimer's disease.