Oxidative DNA damage was measured in the substantia nigra (SN), cortex, hippocampus, striatum and hypothalamus of 3- and 24-month-old rats, using single-cell gel electrophoresis (SCGE, 'comet' assay) which allows the detection of DNA breaks and oxidized bases. A significant increase in basal DNA damage was selectively found in the SN of aged rats. FPG-sensitive oxidative DNA damage was also significantly increased in the SN of aged rats and, to a lesser extent, in the cortex and hypothalamus. These data show a higher vulnerability of SN to oxidative damage with aging and indicate that the detection of DNA damage within discrete brain nuclei can provide a reliable tool for investigating oxidative damage in neurodegenerative processes.