We studied the nature of diffuse type of senile plaques (SP) in the brains of six autopsied subjects with Alzheimer-type dementia (ATD). The densities of SP in the entorhinal cortex were evaluated using serial sections stained by four different methods. Compared with beta protein immunostaining (100% as a reference), the modified Bielschowsky stain (103%) and the periodic acid-methenamine silver (PAM) stain (109%) labeled similar numbers of SP, whereas the Bodian stain labeled only a minor proportion (42%) of these. The vast majority of Bodian-negative plaques were diffuse plaques, which were seen as ill-defined areas of fine fibrillar material after beta protein immunostain with formic acid pretreatment, modified Bielschowsky stain, and PAM stain. They were not stained by Congo red or periodic acid-Schiff stains. Double staining using Bodian and beta protein methods demonstrated that diffuse plaques were free of swollen neurites. Argyrophilia of the diffuse plaques shown by the modified Bielschowsky and PAM stains, became undetectable when sections were pretreated with formic acid. Such treatment made the diffuse plaques immunoreactive to beta protein antiserum, suggesting that diffuse plaques consisted mainly of amyloid, but not neuritic components. The diffuse plaques were distributed in various cortical areas and in the amygdala, and comprised a considerable population of the SP in the ATD brains.