The effect of deer antler extracts (DAA) of Cervus korean TEMMINCK var. mantchuricus Swinhoe on protease activities, oxidant and free radical damages in synovial fluid from rheumatoid arthritis in rats was studied. Rats were i.p. administered with DAA. We have compared (using the same series of experimental samples) the levels of activity of a comprehensive range of cytoplasmic, lysosomal and matrix protease types, together with the levels of free radical induced protein damage (determined as protein carbonyl derivative) and total antioxidant in synovial fluid from rheumatoid arthritis (RA) and DAA-treated rats. Many proteases activities were shown to be significantly increased in RA compared to normal rats. Protease activities (including those enzyme types putatively involved in the immune response, such as dipeptidyl aminopeptidase IV) in plasma were not significantly different between RA and normal rats. DAA treatment at dose of 100 microg/kg suppressed the production of the proteases of cytoplasmic, lysosomal and matrix protease types. The level of free radical induced damage to synovial fluid proteins was approximately 2-fold lower in DAA rats compared to RA rats, although there was no significant difference in total antioxidant status in synovial fluid or plasma between RA and DAA rats. It was concluded that DAA treatment reduces the activation of proteolytic enzymes and free radicals, which are likely to be of equal potential importance as protein damaging agents in the pathogenesis of RA.