The use of nickel-containing alloys in dentistry has been questioned because of the biological liabilities of nickel and the release of nickel ions from dental appliances into the oral cavity. The uptake of nickel by cells in the oral tissues is a critical factor in assessing the biological liabilities of nickel. Nickel uptake by macrophages may be particularly important because of the central role of macrophages in the inflammatory process and the known role of the macrophage in orchestrating the response to biomaterials. The aims of the current study were to assess the reversibility of the uptake of nickel from human macrophages and determine the portion of the nickel which reaches the nuclei as a function of time. Cellular nickel content was measured by means of atomic absorption spectrometry. Nuclear nickel content was assessed after fractionating cells. The results showed that nickel was rapidly taken up by macrophages and that the nickel accumulated in the nucleus in as little as 8 h. After 48 h, over 60% of the cellular nickel was in the nucleus. Once taken up, the nickel was lost at a lower rate. The rate of loss decreased as the initial exposure time to the nickel increased. Thus, the results indicated that macrophages may accumulate nickel if the time between exposures is insufficient to reverse the uptake. Further studies are necessary to correlate the retention of nickel with impaired function of macrophages and to further define the biological risks of using nickel in dental alloys.