OBJECTIVES: Substances such as monomers may be released from composite resin systems and may induce adverse effects in biological tissues. The aim of this study is to investigate the cytotoxic concentrations of resin composite monomers on cultures of human gingival fibroblasts. METHODS: A range of dilutions of five resin composite monomers (HEMA, HPMA, DMAEMA, TEGDMA, and Bis-GMA) were added to the culture medium of human gingival fibroblasts for 24 h. Their cytotoxic effects were measured by using two colorimetric functional assays, mitochondrial dehydrogenase activity (MTT) and lactate dehydrogenase activity (LDH) assay. The logP values (water/octanol partition) of test monomers were also calculated computationally. RESULTS: Mitochondrial reducing activity assessed with the MTT test was inhibited by all monomers and all the monomers increased the LDH release in a reproducible dose dependent manner. A wide range of TC 50 values (concentrations altering MTT and LDH activity by 50%) (0.32-5.8 mM by MTT assay and 0.36-6.7 mM by LDH assay) was observed. Ranking of composite resin monomer cytotoxicities (TC 50) were similar for both the MTT and LDH assays, (Bis-GMA>TEGDMA>DMAEMA>HPMA >HEMA). However, the MTT assay was found to be more sensitive than the LDH assay, particularly when lower doses of the tested monomers were determined. The ranking of TC 50 concentrations correlated with the calculated logP values. SIGNIFICANCE: Monomers used in dental restorative materials show a variety of toxic effects on gingival fibroblasts. A combination approach using MTT and LDH assays provides valuable information about their toxic effects.