Age-related changes in the olfactory system were examined in 22 dogs ranging in age from 10 to 19 years old. Atrophic changes with degeneration were observed in the olfactory epithelium of dogs older than 14 years; the changes were prominent in the dogs over the age of 17 years. Immunohistochemistry using an anti-carnosine antibody, which is a marker for the olfactory cells, demonstrated a decrease in the number of olfactory cells. Electron microscopy also showed a decrease in the number of cilia of olfactory cells and microvilli of supporting cells. Atrophic changes with the features of regeneration were rarely observed in the aged animals. Lipofuscin-like granules in the olfactory epithelium became prominent with age. These age-related changes were similar to those reported in the olfactory epithelium of man and rats. Dystrophic neurites were not detected by a modified Bielschowsky stain or by neurofilament, synaptophysin and tau immunohistochemistry in the olfactory mucosa. There was no beta-amyloid- and ubiquitin-immunostaining in the olfactory mucosa. Senile brain changes, including cerebrovascular amyloidosis, age-related astrocytic gliosis and ubiquitin deposits were found in the olfactory bulb, although neurofibrillary tangles and senile plaques were not detected either by a modified Bielschowsky stain or by beta-amyloid immunohistochemistry. These results indicate that dog may be a useful animal model to study the age-related changes in the olfactory system in man.