Previous cell culture evaluations have shown that nickel-chromium dental alloys did not affect cellular viability or morphology. However, nickel-based alloys released corrosion products which decreased cellular proliferation. It was hypothesized that this decrease was due to an interference of cellular energy metabolism by released metal ions. To test this hypothesis, we evaluated the effects on cellular energy metabolism, adenosine triphosphate (ATP) levels, and cellular ultrastructure by four nickel-based alloys, including high and low chromium alloys with and without beryllium additions, in human gingival fibroblast cell cultures. Energy metabolism was evaluated by measuring glucose-6-phosphate dehydrogenase (G-6-PDH) activity. ATP levels were measured with the luciferin-luciferase method. Cellular membranes and ultrastructural organization were evaluated by scanning and transmission electron microscopy. The results of this study showed that metal ions released from all alloys completely inhibited G-6-PDH activity and reduced cellular ATP levels as compared to controls. The reduction in intracellular ATP was greater for the beryllium containing alloys than the non-beryllium-containing alloys. However, no morphologic changes in cellular membranes or organelles were observed. These results support the hypothesis that metal ions released from nickel-based dental casting alloys interfere with cellular energy metabolism.