In order to elucidate the oxidative effects and genotoxicity of nickel on human lymphocytes in vitro, we report the level of intracellular reactive oxygen species (ROS), lipid peroxidation, hydroxyl radical ((*)OH), and DNA damage in human lymphocytes after acute exposure to inorganic nickel. NiCl(2) appeared to increase the formation of the fluorescent oxidized compound dichlorofluorescein (DCF). Lipid peroxidation in lymphocytes significantly increased compared to control. 2,3- and 2,5-DHB increased markedly in a concentration-dependent manner. Single-strand DNA breakage induced by Ni in lymphocytes was evaluated by Comet assay. Significant increase in DNA damage score (arbitrary units) showed a dose-related elevation after treatment with NiCl(2). NiCl(2) induced lipid peroxidation at 0.5 mM but had no effect on DNA strand breakage. These results support the emerging concept that NiCl(2)-induced oxidative stress and genotoxicity may be caused by oxygen radical intermediates. NiCl(2)-induced DNA strand breakage is related to the generation of the (*)OH radical.