Detailed analyses of the neuropathologic changes in the cerebral cortex of elderly individuals and Alzheimer's disease patients have demonstrated that certain components of the neocortical and hippocampal circuits are likely to be selectively vulnerable. In order to investigate the distribution of lesions associated with aging as well as with the earliest symptoms of Alzheimer's disease, we performed a quantitative neuropathological evaluation of sixty-one non-demented patients from a geriatric hospital. All of the cases had neurofibrillary tangles in layer II of the entorhinal cortex, and many cases had an involvement of the CA1 field of the hippocampus and the inferior temporal cortex. In all of the cases, amyloid deposition was not correlated with age or with the number of neurofibrillary tangles. In addition, eight cases showed much higher neurofibrillary tangle counts than the remainder of the cases. It is proposed that these cases may represent the neuropathological correlate of the earliest stage of Alzheimer's disease that could antedate the appearance of clinical signs of cognitive decline and memory impairment.