In Alzheimer's disease, three types of pathologic lesions are stained by thioflavin: neurofibrillary tangles, senile plaques, and amyloidaceous vessels. We have used anti-beta protein amyloid A4 and anti-tau protein antisera and compared immunolabeling with thioflavin staining. Anti-tau detected only neurofibrillary tangles; anti-beta-PA4 immunostained senile plaques and amyloidaceous vessels. Glycolytic pretreatment (2% periodic acid overnight or glycosidases digestion) dramatically enhanced the anti-beta-PA4 immunolabeling of senile plaques, amyloidaceous vessels, and a previously undetected extracellular substance; neurofibrillary tangles were never immunostained. Therefore, glycolytic pretreatment exposes buried epitopes in the amyloid and is a good method for amplification of immunostaining. The nature of the interaction between saccharides and beta-protein amyloid A4 is unknown.