Abstract: Toxic and carcinogenic effects of nickel compounds are suggested to result from nickel-mediated oxidative damage to macromolecules and/or inhibition of cellular antioxidant defenses. We investigated the effects of waterborne Ni2+ (10, 25 and 50mg/L) on the blood and blood-producing tissues (kidney and spleen) of goldfish to identify relationships between Ni accumulation and oxidative stress. Whereas the main hematological parameters (total hemoglobin and hematocrit) were unaffected, Ni2+ exposure had substantial influence on goldfish immune system, causing lymphopenia. Ni accumulation increased renal iron content (by 49–78%) and resulted in elevated lipid peroxide (by 29%) and protein carbonyl content (by 274–278%), accompanied by suppression of the activities of superoxide dismutase (by 50–53%), glutathione peroxidase (15–45%), glutathione reductase (31–37%) and glucose-6-phosphate dehydrogenase (20–44%), indicating development of oxidative stress in kidney. In contrast to kidney, in spleen the activation of glutathione peroxidase (by 34–118%), glutathione-S-transferase (by 41–216%) and glutathione reductase (by 47%), as well as constant levels of low molecular mass thiols and metals together with enhanced activity of glucose-6-phosphate dehydrogenase (by 41–94%) speaks for a powerful antioxidant potential that counteracts Ni-induced ROS production. Further, as Ni accumulation in this organ was negligible, Ni-toxicity in spleen may be minimized by efficient exclusion of this otherwise toxic metal. [Copyright &y& Elsevier]