DNA damage to peripheral blood lymphocytes of patients with Graves' disease (GD) was studied in vitro before and after treatment with antioxidants, melatonin, quercetin, N-acetylcysteine (NAC) and vitamin C. DNA damage (comet %) was remarkably higher in patients (23.7 +/- 5.5%) than that in healthy persons (9.8 +/- 3.2%, p < 0.01). Plasma malondialdehyde (MDA) content (7.90 +/- 1.77 microM) of patients was significantly higher than that of healthy persons (4.71 +/- 1.19 microM, p < 0.01). Also, the plasma total antioxidant capacity (TAC) (7.53 +/- 1.35 U/ml) in GD patients was significantly lower than that in healthy persons (10.56 +/- 2.21 U/ml, p < 0.01). Negative correlations were observed between plasma TAC and DNA damage in lymphocytes (r = -0.599, p < 0.01), and between plasma TAC and MDA (r = -0.40, p < 0.05) in GD patients. After treatment with 100 microM melatonin, quercetin or NAC for 4 h in vitro, DNA damage in lymphocytes in GD patients declined significantly (from 23.8 +/- 4.4% to 14.4 +/- 4.0%, p < 0.001 for melatonin, from 23.4 +/- 4.7% to 18.1 +/- 4.3%, p < 0.01 for quercetin, from 23.7 +/- 4.0% to 18.7 +/- 5.7%, p < 0.05 for NAC), while there was little change with concentrations of 1-100 microM of vitamin C. However, 1000 microM vitamin C enhanced DNA damage significantly (from 23.8 +/- 2.3% to 30.3 +/- 3.9%, p < 0.05). Our results showed that oxidative stress existed in GD patients and the antioxidants melatonin, quercetin and NAC are beneficial for DNA damage in lymphocytes of GD patients in vitro.