Purpose: The aim of this study was to assess the cytotoxicity of 4 resin composites' eluates on WEHI 13 Var fibroblasts as they aged in a biologic medium. Materials and Methods: Cytotoxicity was determined by counting the number of viable cells by trypan blue exclusion. Morphologic changes attributable to cytotoxicity were observed by May-Grunwald-Giemsa cytologic staining and microscopic examination. DNA gel electrophoresis was performed to detect possible genotoxicity and DNA damage. Results: All resin composite eluates, except that for Targis, caused a pronounced cytotoxicity during the first 72 hours that gradually decreased after 2 weeks of aging. Severe morphologic alterations and pronounced DNA damage were also observed. Conclusion: These findings indicate that resin-based dental restorative materials release agents cytotoxic and genotoxic to fibroblasts. Cytotoxicity is gradually decreased as the composite resins age in a biologic-relevant medium.