The binding site distribution of calcitonin gene-related peptide (CGRP) was studied in the central nervous system of aged rats (22 months old) and compared with that of young rats (2 months). The regional distribution of [125I]Tyr-rat CGRP binding in coronal sections of young and old rat CNS was examined by an in vitro autoradiographic technique. The results, showed that in aged rats there was a marked reduction in CGRP binding, without any change in binding affinity, in the hippocampus, the nucleus rhomboideus, the nucleus arcuatus, the colliculus superior, the substantia grisea centralis and the spinal cord. In the cortical areas, the amygdala, the caudatus putamen and the accumbens binding was not modified. In the cortex cerebellaris CGRP binding was strikingly greater in the aged rats. The increase in binding might be a consequence of an adaptive process due to a decline of the peptide synthesis with age and is suggestive of a role for CGRP in the cerebellum functions.