Cockayne's syndrome is associated with dementia and other physical signs of premature senescence. Death usually occurs in the first or second decade of life. Because previous neuropathologic descriptions have included neurofibrillary tangles and calcific and dystrophic cerebrovascular changes, we examined the mesial temporal lobes of three children with Cockayne's syndrome (confirmed by 254-nm ultraviolet light studies). Immunohistochemistry was used to determine if beta-amyloid immunoreactivity was present in the parenchyma or cerebral blood vessels. Tissues from the mesial temporal lobe of patients with Alzheimer's disease and Down syndrome were used as controls. None of the three temporal lobes from patients with Cockayne's syndrome contained beta-amyloid immunoreactive material in either the parenchyma or vessels; all of the Alzheimer's disease and Down syndrome controls had beta-amyloid immunoreactivity.