Reactive oxygen species have been long associated with oxidative stress relevant to many pathological damages. In brain, 4-hydroxy-2E-nonenal (HNE), a major cytotoxic end product of lipid peroxidation, is produced. In contrast, superoxide dismutase (SOD), one of the major antioxidant enzymes, protects neurons from oxidative stress. The aim of this study is to observe differences in the distribution of HNE and Cu,Zn-superoxide dismutase (SOD1) in the hippocampal CA1 region of adult (2-3 years of age) and aged (10-12 years of age) dogs. The HNE immunoreactivity and protein level in the CA1 region were significantly high in the aged dogs compared to those in the adult dogs. SOD1 immunoreactivity and its protein level were also higher in the aged dogs than those in the adult dogs. However, there were not significant differences in NeuN (a neuron-specific soluble nuclear antigen) immunoreactivity in CA1 neurons between the adult and aged dogs. These differences may be associated with oxidative stress in aged dogs compared to that in adult dogs.