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We studied the biological variability of blood superoxide dismutase (SOD; EC 1.15.1.1), glutathione peroxidase (GPX; EC 1.11.1.9), and catalase (CAT; EC 1.11.1.6) in a sample of 1836 apparently health subjects, ages 4-97 years. SOD and GPX activities were assayed in plasma (P) and erythrocytes (E) by automated methods, and CAT was measured in erythrocytes by a manual technique. No statistically significant variation of these antioxidant enzyme activities according to gender was demonstrated, except for E-GPX, which was slightly but significantly higher in women than in men (P less than 0.001). Activities appear rather stable in adults less than 65 years old, but decrease for most enzymes in the elderly. There is no evidence that weight, blood pressure, or menopause influences the antioxidant enzymes' activities. In girls ages 10-14 years, E-SOD activity is reduced by 16% (P less than 0.05) after menarche. Variations related to smoking and alcohol consumption are slight and concern only P-SOD and P-GPX, respectively. Conversely, intake of some drugs (e.g., anti-inflammatory agents, antidepressants, and thyroid hormones) modifies activity of some of the three enzymes. E-SOD positively correlates with P-SOD (r = 0.216, P less than 0.001) and E-CAT (r = 0.123, P less than 0.001), and E-GPX with P-GPX (r = 0.218, P less than 0.001). Finally, we propose reference intervals for activities of the three antioxidant enzymes in blood in individuals less than 65 years old.