Preparing for a retrospective study of senile degeneration in schizophrenia, we had occasion to explore the suitability of an old collection formalin-fixed brains and paraffin blocks for study by modern staining methods. Tissue that had been in formalin for 50 years was embedded in paraffin. Sections were then stained with thioflavine S and with immunoperoxidase stains using Alz 50 and antibodies to paired helical filaments, ubiquitin, and beta-amyloid. In all 4 cases that had originally (50 years earlier) received neuropathologic diagnoses of Alzheimer's disease, large numbers of neocortical senile plaques and neurofibrillary tangles were clearly demonstrated by thioflavine S stain and by immunohistochemistry for paired helical filaments, ubiquitin, and beta-amyloid. In each of 4 other cases, in which the original neuropathologic examination had not revealed Alzheimer's disease, no plaques or tangles were observed. Immunoreactivity with Alz 50 was completely absent after 50 years in formalin. Examination of additional cases of Alzheimer's disease revealed that Alz 50 immunoreactivity was well preserved after 10 years in formalin and completely absent after 30 years in formalin. Alzheimer's disease tissue stored in paraffin for 30 years was clearly stained by all modalities. We conclude that immunohistochemical identification of senile plaques and neurofibrillary tangles is practical even after decades of storage in formalin or paraffin. The applicability of techniques that did not exist when these specimens were collected indicates that the systematic, permanent retention of formalin-fixed material may yield unanticipated future benefits.