We report here routine thin-section and immunogold electron microscopic studies on diffuse plaques in scrapie-affected hamster brains. These plaques were not discernible by routine H&E staining. Ultrastructurally, plaques were recognized as areas of low electron density containing haphazardly-oriented fibrils, but not as stellate compact structures typical of mouse scrapie models; hence we labelled them “loose plaques”. Following immunohistochemistry at the electron microscopy level, fibrils within plaques were heavily decorated with PrP-conjugated gold particles. Loose plaques were located beneath the basal border of the ependymal cells and around blood vessels in the adjacent subependymal neuropil. When dystrophic neurites containing electron-dense inclusion bodies, some of them autophagic vacuoles [59], were seen within the plaque perimeter, they always remained PrP-negative. Some microglial cells were observed in close contact with PrP-positive plaques, and secondary lysosomes within these cells were heavily decorated with gold particles.