The excess of genetic information in patients with Down's syndrome (DS) produces an increase in the catalytic activity of superoxide dismutase (SOD1), an antioxidant enzyme coded on chromosome 21. It has been suggested that an increase in oxidative stress in DS patients may cause adverse effects in the cell membranes through the oxidation of polyunsaturated fatty acids (PUFAs). The aim of this study was to evaluate the cellular antioxidant system by determining the catalytic activity of the SOD1, glutathione peroxidase (GPx), catalase (CAT), and glutathione reductase (GR) enzymes and the concentrations of alpha-tocopherol in red blood cells (RBCs) in a group of 72 DS patients. The profile of fatty acids in the phospholipids of RBC membranes was also evaluated. The activity of the erythrocyte antioxidant enzymes is significantly higher in the DS group than in the control group (SOD1, 635 +/- 70 U/g Hb vs 476 +/- 67 U/g Hb; CAT, 1843 +/- 250 U/g Hb vs 1482 +/- 250 U/g Hb; GPx, 23.2 +/- 5.3 U/g Hb vs 21.5 +/- 3.6 U/g Hb; and GR, 9.32 +/- 1.4 U/g Hb vs 6.9 +/- 1.3 U/g Hb, respectively). No differences were observed in RBC alpha-tocopherol concentrations between the two groups studied. Long-chain n6 PUFA (C20:3n6, C20:4n6) concentrations were increased in DS patients, suggesting enhanced delta-6-desaturase activity. The long-chain n3 PUFA (docosahexenoic acid) does not appear to be affected by increased oxidative stress, probably because of the existence of compensatory antioxidant mechanisms.