We investigated the age-related changes in the tissular protein, cortico-releasing factor (CRF), somatostatin (SOM), neuropeptide Y (NPY), methionine enkephalin (M-ENK) and β-endorphin (β-END) levels in frontal cortex, hippocampus, striatum and hypothalamus of young (4-month-old), mature (18-month-old) and senescent (26-month-old) Wistar male rats, bred in a specific pathogen free environment. Between the age of 4 and 18 months, the tissular protein levels increased in all 4 structures studied. The CRF and SOM levels increased in the hippocampus, while the NPY levels decreased. During this time, the NPY content increased in the striatum, whereas the SOM and M-Enk striatal levels decreased. Concomitantly, the NPY and β-End levels decreased in the hypothalamus. Interestingly, no significant variations were found to occur in the frontal cortex whatever the neuropeptide studied. Between the age of 18 and 26 months, no significant changes in the tissular protein levels were detected, except in the hippocampus. The changes in the neuropeptide concentrations observed during this period depended on the neuropeptide and the brain structure studied. The CRF and β-End levels decreased in the frontal cortex and the hypothalamus, respectively. The NPY peptidergic systems seem to be preferentially affected by aging processes since 3 out of the 4 structures studied — the frontal cortex, the striatum and the hypothalamus — showed a decrease in their tissular NPY content. During the same period, none of the 5 neuropeptides studied were affected in the hippocampus.