This study evaluated the gender differences in response to intense exercise on lymphocyte hydrogen peroxide production, nitric oxide handling and mitochondrial superoxide dismutase (MnSOD) activity and gene expression. Fifteen males and nine females participated voluntarily in the study and performed a swimming session at 75-80% of the maximal capacity. In basal conditions females presented higher lymphocyte MnSOD activity compared to males (p<0.05). Exercise increased MnSOD activity in males (p<0.05) reaching similar values to females. MnSOD gene expression was also increased in males after exercise (p<0.05) but not in females. Nitrite concentration and iNOS gene expression significantly increased only in males after swimming (p<0.01). The exercise decreased UCP-3 gene expression in both genders (p<0.05). Lymphocyte H(2)O(2) production significantly increased in males after exercise in non-stimulated and in PMA-stimulated cells (p<0.01). In conclusion, females seem to be more protected against oxidative stress induced by a swimming session. Hydrogen peroxide is mainly produced in males and this subsequently leads to increases in MnSOD gene expression and activity.