In subjects with Down's syndrome (DS) increased oxidative stress and consequent oxidative cell damage have been reported. The aim of this study was to assess whether the excessive production of free oxygen radicals in these subjects can affect the copper-induced lipid oxidation resistance measured in fresh whole serum. Since a significant elevation of serum uric acid levels, which is an efficient hydrophilic antioxidant, has been repeatedly reported in subjects with DS, we studied the association between increased serum uric acid levels and lipid resistance to oxidation measured directly in serum samples by monitoring the change in absorbance at 234 nm. The group of subjects with Down's syndrome consisted of 25 individuals (aged 18+/-5 years). Control group included brothers and sisters of subjects with DS (n = 25, aged 17+/-7 years). In subjects with DS, the serum lipid resistance to oxidation (lag time) was significantly higher than in controls (p<0.05) and a concomitant increase in serum uric acid levels was observed (p<0.001). A significant positive correlation between lag time and serum uric acid concentration was found in subjects with DS (r = 0.48, p<0.05), while the positive correlation in the control group was not significant. The results suggest that increased serum uric acid levels repeatedly observed in subjects with DS may be associated with an enhanced resistance of serum lipids to oxidation which is thought to play an important role in the atherogenic process.