The effects of exposure of early-passage Syrian hamster embryo cells in culture to sodium fluoride have been studied with respect to induction of morphological and neoplastic transformation, chromosome aberrations, sister chromatid exchanges, and unscheduled DNA synthesis. Exposure of Syrian hamster embryo cells to NaF concentrations between 75 and 125 micrograms/ml for 24 hr caused approximately 90 to 40% cell survival and resulted in a dose-dependent increase in the frequency of morphological transformation of the cells. Mass cultures of cells treated with NaF (75 or 100 micrograms/ml) for 24 hr, followed by continuous cultivation for 35 to 50 passages, developed the ability to grow in soft agar and to produce anaplastic fibrosarcomas when injected into newborn hamsters. In contrast, no morphological and neoplastic transformation was observed in untreated cells. Furthermore, a significant increase in chromosome aberrations at the chromatid level, sister chromatid exchanges, and unscheduled DNA synthesis was induced by NaF in a dose- and time-dependent manner. These results indicate that NaF is genotoxic and capable of inducing neoplastic transformation of Syrian hamster embryo cells in culture. A potential for carcinogenicity of this chemical, which is widely used by humans, is suggested. However, the carcinogenic risk of this chemical to humans may be reduced by factors regulating in vivo dose levels.