Tissue damage caused by oxidative stress has been implicated in aging, carcinogenesis, atherosclerosis and neurodegeneration. In xeroderma pigmentosum (XP) and Cockayne syndrome (CS), oxidative stress is associated with promoted occurrence of skin cancers and progressive neurodegeneration, because decreased DNA repair and persistent DNA damage can result in augmented oxidative nucleotide damage. Oxidative nucleotide damage has been investigated mainly in isolated human skin and blood cells or their cell lines, in which CS cells may be more sensitive to oxidative DNA lesions than XP cells. However, cells from patients with XP group A (XPA) show defective repair of 8, 5'-(S)-cyclo-2'-deoxyadenosine, a free radical-induced endogenous DNA lesion and antioxidant system seems to be disturbed variously in cells from XP patients. We have neuropathologically investigated the involvement of oxidative stress in the brains of XPA and CS autopsy cases and clarified the enhanced lipid peroxidation and protein glycation in the pallidal and cerebellar degeneration. Also, oxidative nucleotide damage with reduced expression of superoxide dismutases has been identified in the basal ganglia lesions, lending further weight involvement of oxidative stress in neurodegeneration in XPA patients. Additionally, we are developing ELISA analysis of oxidative stress markers in the urine and cerebrospinal fluid from XP patients, which will aid with further data on oxidative stress in pathogenesis of XP.