Carp head kidney (HK) phagocytes can be stimulated by lipopolysaccharide (LPS) to produce nitric oxide (NO). High production of NO can suppress the carp immune system. Carp peripheral blood leukocytes (PBL) are highly susceptible but HK phagocytes are relatively resistant to the immunosuppressive effects of NO. This study demonstrates that the antioxidant glutathione plays an important role in the protection against nitrosative stress. Carp HK phagocytes, especially the neutrophilic granulocytes, contain higher levels of glutathione than PBL. Moreover, freshly isolated carp neutrophilic granulocytes have higher mRNA levels than PBL of glucose-6-phosphate dehydrogenase (G6PD), manganese superoxide dismutase (MnSOD) and gamma-glutamylcysteine synthetase (gamma-GCS). Since these molecules are part of the glutathione redox cycle, neutrophilic granulocytes have a higher capacity than PBL to maintain glutathione in a reduced state following nitrosative stress. When stimulated with LPS, neutrophilic granulocytes upregulate the expression of G6PD, MnSOD and gamma-GCS.