We used single photon emission computed tomography with the blood flow tracer [123I]N-isopropyl-p-iodoamphetamine (IMP) to study regional cerebral blood flow (rCBF) in 50 mildly and moderately demented Alzheimer's disease (AD) patients to evaluate rCBF as a function of disease severity. Relative rCBF (normalized to occipital cortex) was significantly lower than controls in temporal cortex for both mildly and moderately demented patients. Similar numbers of patients in both groups demonstrated perfusion abnormalities in temporal neocortex. Parietal cortex was more variably involved with greater numbers of moderately than mildly demented patients showing perfusion abnormalities. Relative rCBF in dirsolateral frontal cortex was reduced only in the moderately demented patients. Disease severity, as measured by the Mini Mental Status Examination, was associated with relative rCBF only in dorsolateral frontal and parietal cortex. These results suggest that the temporal lobes are the first neocortical regions affected by AD and that other cortical areas become involved as the disease progresses.