We report here the microglial (macrophage) and astrocytic reaction in several models of transmissible spongiform encephalopathies (TSEs) or prion diseases. With the low power electron microscopy it was readily apparent that myelinated vacuoles were surrounded by cells and their processes. The latter belonged either to hyperplastic reactive astrocytes or to macrophages. Typically reactive astrocytes exhibited cytoplasm filled with innumerable glial filaments and, occasionally, other organelles (like cilia) and abundant tortuous intercellular junctions of adhesive plaque junction type. Desmosome-like junctions connecting astrocytic elements were also seen. As described earlier, astrocytic processes were occasionally interdigitated with oligodendroglial cells and their processes. Two types of macrophages were readily described. The majority of them exhibited electron-dense cytoplasm and numerous ?empty? vacuoles (digestive chambers) containing cellular debris. Occasional vacuoles were surrounded by a thin collar reminiscent of ?lyre-like inclusions? of the second type of macrophages. The latter were rare and characterized by numerous ?lyre-like? inclusions. Several mylinated fibres were clearly engulfed by the cytoplasm of a macrophage containing unusual annulate lamellae.