Although Alzheimer's disease is generally considered a degenerative disease that primarily affects the cerebral cortex, subcortical structures such as the substantia innominata and certain brainstem nuclei may be involved. In 28 patients with progressive dementia and pathologically confirmed Alzheimer's disease, we found senile (neuritic) plaques and neurofibrillary tangles in the thalamus in 25 patients, in the hypothalamus in 22, and in the mamillary body in 17. The severity of these lesions seemed to be greater in those with presenile onset of dementia, but was not related to the duration of dementia. Alzheimer's disease is a much more diffuse disorder than is usually appreciated.