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 dental alloy–treated groups. Conclusion: Taken together, it is possible to postulate that Ni-Cr and Co-Cr dental alloys, especially sandblasted forms, may have detrimental effects on the actin-based cytoskeleton, at least tested in vitro. Int J Prosthodont 2004;17:45–51.