Recent studies have explored certain changes with aging of neurons containing neuropeptides. The degree of loss of vasoactive intestinal polypeptide (VIP)-, neuropeptide Y (NPY)- and somatostatin-containing neurons in the aged CNS has not yet been established with certainty however, and available data is often contradictory. Changes with aging of VIP- and NPY-containing neurons were demonstrated by immunocytochemistry in this study. A major loss of VIP-immunoreactive (ir) neurons in aged rat brain was observed in the frontal cortex area 3, parietal cortex area 1, hindlimb area, temporal cortex area 1 and 2, monocular part of occipital cortex area 1, occipital cortex area 2, and retrosplenial cortex. VIP-ir cells in the frontal cortex areas 1 and 2, parietal cortex area 2, forelimb area, binocular part of the occipital cortex area 1, and the dentate gyrus were moderately decreased. The axis of VIP neurons in the aged group showed an irregular orientation tendency, especially in layers II and III. Major loss of NPY-ir neurons in aged rat brain were observed in the retrosplenial cortex, frontal cortex areas 1 and 2, parietal cortex areas 1 and 2, occipital cortex areas 1 and 2, the temporal cortex, hippocampus proper and cingulate cortex. Loss of NPY-ir neurons was observed mostly in layers V and VI. The number and length of dendritic branches also appeared to have decreased and shortened in the aged group. There were only slight decreases of somatostatin-ir cell numbers in the parietal and occipital cortex of the aged group. These results indicate the involvement of VIP and NPY-ir neurons in the aging process of cerebral cortex, and provide the morphological evidence for the decreased number of VIP and NPY neurons by immunocytochemistry in each area of cerebral cortex of aged rats.