We compared the ultrastructure between diffuse and primitive plaques in the brains of senile dementia, using pairs of routine electron microscopic ultrathin sections and adjacent semithin sections, which were immunolabeled for beta protein. In the frontal cortex, amyloid fibrils were rarely seen in a minority of diffuse plaques, suggesting an initial stage of the diffuse plaques. A majority of the diffuse plaques had electron-dense material and/or amyloid fibrils between cell processes in part of but not the entire beta/A4-immunoreactive areas. Small degenerating neurites were often seen with apparent amyloid fibrils in the diffuse plaques, and these were considered to be in an advanced stage. The size and number of degenerating neurites were proportional to the amount of amyloid. Bundles of amyloid fibrils were occasionally surrounded by astroglial processes forming gap junctions. Neurons were found within some diffuse plaques, but capillaries were rarely seen. In contrast, in the temporal cortex, the diffuse plaques were smaller, and even these small ones had apparent amyloid fibrils. The amount of amyloid correlated significantly with plaque size in the temporal cortices, but not in the frontal cortices. Most of the diffuse plaques of the frontal lobe remained as advanced diffuse plaques (apparent amyloid with occasional astroglia and some degenerating neurites) for a long time, and did not transformed into primitive plaques, whereas the temporal diffuse plaques tended to transform into primitive plaques.