In an oral environment, minute amounts of constituent metals dissolve from the surfaces of restorations. The uptake of the metals through the mucosa may cause systemic or local effects. The purpose of this study was to investigate these effects and mechanisms, focusing on the nickel as a dental metal. A nickel-chromium dental casting alloy was stored in 3 immersion solutions for 4 weeks and the amount of nickel dissolved was measured. NiCl2 was administrated to the cultured medium to examine the cytotoxicity for HeLa cells and periodontal ligament-derived cells as well as the nickel distribution in the HeLa cells. The results were as follows: 1. The amounts of nickel released from the alloy were 1.2 micrograms/cm2 (human saliva), 2.0 micrograms/cm2 (PBS (-)) and 2.5 micrograms/cm2 (MILLI-Q water). 2. 3.0 mM NiCl2 showed a large cytotoxicity resulting in the cell growth rate and morphological changes. 3. Incubated for 72 hours in 0.15 mM NiCl2, the amount of nickel in the 10(6) cells was 20 ng. After 24 hours of incubation with NiCl2, and the following 72 hours without NiCl2, the amount of nickel had decreased, but 30% still remained. 4. Incubated for 72 hours in 0.15 mM NiCl2, 65% of the nickel in the cells was bound by the soluble fraction. These results suggest that nickel released from the oral prosthesis may be sequestered for a long term in the cells and possibly causes some effects.