We aimed to determine the importance of neutrophil activation and the source of oxidative stress in the pathogenesis of rheumatoid arthritis (RA) by quantification of advanced oxidation protein products (AOPP) and total thiol levels as markers of oxidative protein damage, malondialdehyde (MDA) levels as a marker of lipid peroxidation and myeloperoxidase (MPO) activity as a marker of neutrophil activation in patients with RA. Fifty-seven rheumatoid arthritis patients were included in the study and sub-grouped according to disease activity (active, n ¼ 31; inactive, n ¼ 26) and compared with healthy controls (n ¼ 25). Serum MPO activity, AOPP, MDA, and thiol levels were measured by an enzymic spectrophotometric method. Serum MPO activity ( p < 0.001), AOPP ( p < 0.001), MDA ( p < 0.001) and levels of thiol ( p < 0.002), were higher in the patient group than the controls. Active and inactive RA groups were compared with the control group and there were significant differences between each parameter. MPO activity, AOPP, MDA and thiol levels were significantly higher in both active and inactive RA patients than the controls. On the other hand, when a comparison was made between active and the inactive stage, a statistically significant difference was present only in MDA ( p < 0.05) and AOPP levels ( p < 0.05). There was also a significant positive correlation between all parameters. These data strongly suggest that neutrophils, which constitute the most important source of chlorinated oxidants due to their high MPO content, may be involved in serum AOPP formation and therefore the production of a novel class of pro-inflammatory mediators of oxidative stress in RA patients and that protein oxidation could play an important role in the pathogenesis of RA as does lipid peroxidation.