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Cell culture is a valuable method of evaluating the biocompatibility of new dental materials. The purpose of this study was to compare the in vitro biocompatibility of an experimental fluoride composite resin with fluoride and non-fluoride-releasing materials currently available. The dental materials tested were: MQ Silicate (silicate cement), KETAC-CEM and FUJI (type II glass ionomer cements), VISIO DISPERS (a light-cured, nonfluoridated, microfilled composite resin), and FR-17 (an experimental fluoride-releasing composite resin). The Smulow-Glickman (S-G) human, gingival epithelial cell line, which exhibits semidifferentiated characteristics, was used in the study as a test system. Biocompatibility was quantified by counting the viable cells per unit area remaining after 24 and 48 h at two radial distances from cured specimens immersed in the cell culture medium. The test materials were observed to be most toxic to cells nearest the materials. A Time-Distance Cytotoxicity Index (TDCI) was calculated to relate the percentage of dead cells to viable cells at each diffusion distance for each exposure time compared to a nontoxic control. The relative toxicity ranking of the materials tested based on the TDCI was VISIO DISPERS (91%), FUJI (82%), FR-17 (30%), MQ Silicate (23%), and KETAC-CEM (10%), which exhibited the least toxicity. The cytotoxicity of the experimental resin FR-17 was within the range of cytotoxicity of currently accepted restorative materials.