Examination of the thalamic reticular nucleus (Rt) with the monoclonal antibody Alz-50 in brains of Alzheimer's disease patients reveals dense extracellular and terminal-like immunoreactivity in the absence of neurofibrillary tangles or neuritic plaques. Similar terminal-like immunoreactivity is not present in other thalamic nuclei of AD brains or in the brains of controls. Based on (1) an immunocytochemical and histopathological analysis of areas known to project to the Rt, (2) that Alz-50 immunocytochemistry reveals immunoreactive neurons, neurofibrillary tangles and neuritic plaques, and (3) evidence that Alz-50 immunoreactivity can be demonstrated in the terminal fields of immunoreactive neurons, the terminal-like immunoreactivity in the Rt probably corresponds to altered preterminal axons and terminals from degenerating basal forebrain neurons. Given the presumed physiological role of the Rt, these selective lesions could alter thalamocortical processing and contribute to the cognitive impairment in Alzheimer's disease.