The immunohistochemical localization of amyloid beta/A4 protein in the senescence-accelerated mouse brain was studied using six different antisera against human amyloid precursor protein peptides. beta/A4 proteinlike immunoreactivity was observed in the form of granular structures (beta-LIGS) in various regions, including the medial septum, cerebral cortex, hippocampus, cerebellum, and some cranial nerve roots. beta-LIGS were 1.5 to 2.5 mu in diameter and irregularly shaped. They increased significantly in number with aging, predominantly in animals with a phenotype of age-related deterioration of memory and learning abilities. Congo red and thioflavine S did not stain the granules. On immunoblots, the main immunoreactive bands were observed at 14 to 18 kd. The staining intensities of these bands also increased with advancing age. We consider that beta-LIGS are not only a new morphological manifestation of senescence in mice, but also a pertinent clue in understanding the mechanisms of amyloid deposition.