Objectives: To investigate the toxicity of 4 types of resin-based dental composites with different compositions and to determine the components released from them using high-performance liquid chromatography (HPLC). Method and Materials: Resin composite disks (Z100, Solitaire 2, Filtek P60, and Synergy) were prepared, and cytotoxicity was tested on Balb/C 3T3 fibroblasts. In the first part of the study, cells were exposed to the composites for 72 hours (direct method), and in the second part to ethanolic extracts of the composites for 24 hours (indirect method), both at 37°C. Cell viability was then determined by the MTT (3[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) method. Results: The dental composites and their ethanolic extracts had adverse effects on the viability of Balb/C 3T3 fibroblasts. ANOVA revealed highly significant differences in cytotoxicity between the groups (P .001) for both the direct and indirect methods. Follow-up comparison by Tukey test (a = .05) showed that Synergy was significantly less toxic than the other resin composites and Solitaire 2 was significantly more cytotoxic when the materials were tested by the direct method. However, using the indirect method, the extract of Synergy was significantly more toxic than all the other extracts. Bis-GMA, TEGDMA, UDMA, bis-EMA, and bisphenol A were detected by HPLC analysis; however, their presence and concentrations varied from one composite to another. Conclusions: The cytotoxicity level of resin-based dental composites depends on their chemical composition, leaching medium, and the amount and type of the components that can be extracted from the materials. Keywords: cytotoxicity, leached components, resin composite