An increase in oxidative stress may contribute to the development of oxidative protein damage in the aging rat brain. In the present study, we investigated the relation between nitrotyrosine levels and other oxidative protein damage parameters such as protein carbonyl and protein thiol, as well as oxidative stress parameters such as total thiol, nonprotein thiol, and lipid hydroperoxides in the brain tissue of young, adult, and old Wister rats. Brain nitrotyrosine levels of old rats were significantly decreased compared with those of young rats. Young and adult rats were not significantly different as far as these parameters were concerned, however, brain protein carbonyl and lipid hydroperoxide levels of old rats were significantly increased compared with those of young and adult rats. On the other hand, brain tissue total thiol, nonprotein thiol, and protein thiol levels of old rats were significantly decreased compared with those of young and adult rats. The strong correlation we found between protein carbonyl and lipid hydroperoxide levels indicates a striking relation between protein oxidation and lipid peroxidation in the aging brain tissue. The results of this study suggest that protein carbonyl formation is both a sensitive and a specific marker of brain aging. However, decreased nitrotyrosine levels in old rats, in contradiction to the expected, may be due to mechanisms other than oxidative protein damage in the aging rat brain. (C) 2001 Elsevier Science Inc. All rights reserved.