Changes in the cocentrations of nervous tissuerelated proteins and their isoproteins, such as S‐100 proteins (S‐100α and S‐100β), enolase isozymes (α‐enolase and γ‐enolase), and GTP‐binding proteins (Goα, Gi2α, and β‐subunits), were determined in the CNS of male rats of various ages (from 2 to 30 months old) by means of enzyme immunoassay. The weights of brains and the concentrations of soluble proteins in the cerebral cortex, cerebellum, and brainstem were constant during the observation period. The concentration of S‐100β protein, which is predominantly localized in glial cells, increased gradually in the cerebral cortex with age; levels in the 25‐month‐old rats increased to approximately 150% of the levels in the young (2‐month‐old) rats. However, the S‐100β concentrations in the cerebellum and brainstem were relatively constant, showing similar values in rats 2–30 months old. Levels of other proteins, including both neuronal (γ‐enolase and Goα) and glial (α‐enolase and S‐100α) marker proteins, did not change significantly with age in the cerebral cortex, cerebellum, and brainstem. These results suggest that there is a close relation between the age‐dependent changes of the CNS function and S‐100β protein levels in the cerebral cortex. Copyright © 1990, Wiley Blackwell. All rights reserved