We classified senile plaques (SP) into 4 types: diffuse, primitive, classic, and compact. Here, we studied the nature of diffuse plaques in the brains of 6 autopsied subjects with senile dementia of the Alzheimer type (SDAT). In the entorhinal cortex, both the modified Bielschowsky stain (108%) and periodic acid-methenamine silver (PAM) stain (111%) revealed a number of SP similar to that labeled by beta protein immunostain (100% as standard). The Bodian stain, however, labeled only a minor proportion (37%) of SP. The vast majority of Bodian-negative plaques, which were devoid of swollen neurites, were diffuse plaques. They were seen as ill-defined areas of fine fibrillar materials. Diffuse plaques were argyrophilic when labeled by the modified Bielschowsky and PAM stains. However, they became undetectable when sections were pretreated with formic acid. Formic acid pretreatment made the diffuse plaques immunoreactive with beta protein antiserum. Alzheimer's neurofibrillary tangles (ANT) and the neuritic components of the primitive and classic plaques remained argyrophilic even after pretreatment with formic acid. Our findings suggest that formic acid pretreatment selectively abolishes the argyrophilia of the amyloid-related component of SP, and the diffuse plaques consist mainly of amyloid-related, while the neuritic component does not. Positive reaction products for beta protein were scattered in the SP by immunoelectron microscopy. Some of the reaction products labeled 10 nm filaments resembling amyloid fibrils.