Preliminary data support the hypothesis that the decline of all higher cognitive functions in senile dementia of the Alzheimer type is attributable to histopathological changes in the hippocampal formation, with or without neocortical neuronal lesions. Previous literature amply supports the critical role of this "locus minoris resistentiae" in memory processing and cognitive physiology. New observations include quantitative morphometric evaluations of the hippocampal formation from a longitudinal study of prospectively tested patients and histological and neurochemical data from patients with a clinical presentation consistent with typical Alzheimer's disease, in whom the only neuropathological abnormality was devastating nerve cell loss and gliosis in the hippocampi.