Purpose: The present study was designed to determine the cytotoxic effects of some widely used dental base-metal casting alloys (Ni-Cr and Co-Cr) on the cytoskeleton in cultured human fibroblasts, and to evaluate whether any structural alteration is associated with the application of these alloys. Materials and Methods: Ten specimens from six different alloys were prepared as 5-mm disks. Five of ten samples from each group were polished; the remaining five samples were left sandblasted with 50-µm Al2O3. All samples were directly exposed to human fibroblasts in a 24-well cell culture dish for 120 hours. Then, cells were fixed and stained with antibodies against major cytoskeletal elements-actin, vimentin, and microtubules-by immunofluorescent staining methods. Cells were analyzed in 3-D to document the cytoskeletal alterations using a laser confocal microscope. Results:Disintegration of actin filaments was observed in lamellipodia of fibroblasts by the effect of both polished and sandblasted Ni-Cr and Co-Cr samples, with the exception of the polished Co-Cr alloy (Wirocast). Moreover, intracytoplasmic actin-decorated stress fibers were found bent and occasionally tangled in the sandblasted Ni-Cr (Wiron 99) and Co-Cr alloys (Wirocast and Co-Cr Degussa). Vimentin, a mesenchymal cell intermediate filament protein normally showing an intracellular meshwork pattern, was not affected by any of the polished or sandblasted alloys. Microtubules mainly remained intact in all dentalalloy-treated groups. Conclusion: Taken together, it is possible to postulate that Ni-Cr andCo-Cr dental alloys, especially sandblasted forms, may have detrimental effects on the actin-based cytoskeleton, at least tested in vitro.