The purpose of this study was to clarify the cytotoxicity of Ni2+ ions against murine peritoneal exudate cells (PEC) (macrophages). First, we examined the cell viability of PEC with and without lipopolysaccharide (LPS) stimulation in culture media containing Ni2+ ions up to 1000 micromol/L. Results showed that the cytotoxicity of Ni2+ ions against PEC was dose-dependent and accelerated by LPS stimulation, especially in media with Ni2+ ions exceeding 100 micromol/L. Second, we measured the production of nitric oxide (NO) from PEC and found that LPS caused the PEC to produce abundant NO. However, high dose of Ni2+ ions at concentration more than 200 micromol/L hindered and inhibited NO production. These results pointed out that the cytotoxicity of Ni2+ ions against macrophages depended on both the Ni2+ ion concentration and the presence of bacteria with LPS. Further, NO--a killer of bacteria--was lost when LPS-stimulated macrophages were exposed to high dose of Ni2+ ions.