Morphometric glial fibrillary acidic protein (GFAP) studies of the brains of 11 old (18–29 months) female, outbred athymic mice demonstrated astrocytic gliosis (increase in GFAP-positive astrocytes; GFAP-PA) in all mice with a consistent distribution pattern. Specific areas such as the central white matter, hippocampus, diencephalon, gray matter at the floor of the 4th ventricle, and posterior colliculi showed the change most conspicuously, revealing GFAP-PA both interstitially and perivascularly. There was no apparent demyelination in the affected white matter. In addition, there was an increase in GFAP-PA in the external limiting membrane surrounding the diencephalon and base of brain stem, but only to a minor degree over the cerebral hemispheres. The cerebral and cerebellar cortices and hypothalamus showed no significant increase. In contrast, all of the 2-month-old control animals showed only minor amounts of GFAP-PA, seen in the external limiting membrane and a trace in the cerebral white matter. The present data suggest that astroglial sclerotic change in various regions of the brain is an important morphological expression of cerebral aging. In view of the lack of other demonstrable histological changes (i.e., silver and amyloid stains were negative) or significant atrophy, the cause of the observed gliosis in BALB/c mice might represent a genuine aging change. As an incidental finding, aggregates of PAS-positive granules were noted in the Ammon's horn of most old animals, while none were seen in the young controls.