S100beta is a soluble calcium binding protein released by glial cells. It has been reported as a neurotrophic factor that promotes neurite maturation and outgrowth during development. This protein also plays a role in axonal stability and in long term potentiation in the adult brain. The ability of S100beta to modulate neuronal morphology raises the important question whether there is an age-related difference in the expression of S100beta in the cerebral and cerebellar cortices of AKR strain mice and is this change is region specific. Our RT-PCR and Western blotting experiments show that the expression of S100beta gene in the cerebral and cerebellar cortices starts from 0 day, peaks at about 45 days. However, in 70-week old mice its expression is significantly up-regulated as compared to that of 20-week old mice. S100beta follows the same age-related pattern in both cerebral and cerebellar cortices. These results suggest that S100beta is important for brain development and establishment of proper brain functions. Up-regulation of S100beta in old age may have some role in development of age-related pathological systems in the brain.