The purpose of this study is hopefully to clarify the ambiguity raised in preliminary reports as to gender dependency of oxidative damage in brain proteins. In the current study. we investigated the relation between protein hydroperoxide levels and other protein oxidation parameters. Our study also covered other oxidative stress parameters, such as 4-hydroxynonenal, malondialdehyde, and the redox index in brain tissue of the aged rats. Protein hydroperoxide, 4-hydroxynonenal, thiol levels of male rats were significantly higher than in the female rat group. On the other hand, other oxidative stress parameters were all found to be not different. We suggest that increased total thiol and protein thiol levels found in our study may point to an adaptive reaction to oxidative protein damage. We are of the conviction that the increased thiol groups that we have determined in aged male rats may be a limiting factor in propagation of protein oxidation, as the protein carbonyl, advanced oxidation protein products and nitrotyrosine levels in the brain tissue were unchanged. It has thus been found that gender indeed affects the oxidation of brain proteins and thus its aging; though the extent of the underlying mechanisms affecting brain aging and its etiology are still obscure. (C) 2009 Elsevier Ireland Ltd. All rights reserved.