Immunological disturbances have been reported in thalassemia and the possibility has been raised that these may be consequences of blood transfusion and iron overload. These disturbances are augmentation of the number of supressor T cells (CD8), decreased number and activity of helper T cells (CD4) and impaired activity of NK (natural killer) cells. Iron overload causes toxic tissue changes through the release of free radicals and induces oxidative stress. According to Fenton and Haber-Weiss reactions, iron plays a catalytic role occuring hydroxyl radicals (OH*) which are very reactive free radicals. Antioxidants, like vitamin E, vitamin C and selenium, may modulate oxidative damage.In the present study; firstly, normal lymphocytes mitogen responses and NK activity were investigated by colorimetric MTT test in 26 thalassemia patients and 10 healthy volunteers as control. Secondly, lymphocytes were incubated with vitamin E ( 150, 50, 15 mg/ml), vitamin C (200, 100, 20mg/ml) and selenium (10−5, 10−6, 10−7 M). Finally, lymphocytes mitogen responses and NK activity are investigated. The results were statistically analyzed comparing with controls and healthy volunteers.It was found decreased NK activity of thalassemia patients in comparison with healthy volunteers. The concentration of 10−7 M of selenium enhanced NK activity at the E:T (effector/target) ratio of 50:1 The concentration of 200 mg/ml of vitamin C enhanced NK activity at the E:T ratio of 10:1, 25:1 and 50:1. However, vitamin E decreased NK activity of both thalassemia patients and healhty volunteers. The concentration of 50 mg/ml vitamin E decreased NK activity at the E:T ratio of 5:1 in thalassemia patients and the concentration of 15 mg/ml of vitamin E decreased NK activity at the E:T ratio of 5:1 in healhty volunteers.It was not found any differences between thalassemia patients and healthy volunteers in lymphocytes mitogen responses. The concentration of 200 mg/ml of vitamin C decreased lymphocytes mitogen response against PHA.In conclusion, we suggest that vitamin C and selenium supplementation are required in patients with thalassemia for augmentation of NK cell activity.