To clarify the neuropathological significance of the deposition of N(epsilon)-carboxymethyl lysine (CML), an advanced glycation endproduct, in astrocytic hyaline inclusions in familial amyotrophic lateral sclerosis (FALS), autopsy specimens from five members of two different families who had the superoxide dismutase 1 (SOD1) gene mutations were analysed. Immunohistochemically, most of the neuronal and astrocytic hyaline inclusions were intensely stained by the antibody against CML. The distributions and intensities of the immunoreactivities for CML and SOD1 were similar in the inclusions in both cell types. Immunoelectron microscopy showed that both inclusions consisted of CML-positive granule-coated fibrils and granular materials. No significant CML or SOD1 immunoreactivity was observed in the neurons and astrocytes of the normal control subjects. Our results suggest that astrocytic hyaline inclusions contain CML and SOD1 in FALS patients with SOD1 gene mutations, and that the formation of CML-modified protein (probably CML-modified SOD1) is related to the cell degeneration.