Sequential treatment of Syrian hamster embryo (SHE) cells with a chemical carcinogen followed by sodium fluoride (NaF) resulted in a higher yield of morphologically transformed cell colonies than treatment of the cells with carcinogen alone. For example, cells treated with benzo[a]pyrene (B[a]P; 3 micrograms/ml) for 3 days, then with NaF (25 micrograms/ml) for 4 days, exhibited a transformation frequency more than six times greater than that obtained by summing the transformation frequencies from cells treated with either B[a]P or NaF alone. This enhancement/promotion of cell transformation by NaF was only expressed after the cells had been pretreated with either direct-acting carcinogens or procarcinogens. Pretreatment of the cells with noncarcinogens or weakly-acting carcinogens or administration of NaF prior to treatment with the carcinogen failed to enhance the yield of transformation. Transformation was enhanced even when the NaF treatment was delayed for several days after the carcinogen treatment. However, the continued presence of NaF was necessary for maintenance of the increased level of transformation. Removal of NaF prior to termination of the assay resulted in a reversal of the transformed clonal morphologies to a normal phenotype such that the final yield of transformants was decreased, but was still greater than that observed after carcinogen treatment alone. A similar pattern for reversibility of the transformation enhancement also occurs for the widely recognized tumor promoter phorbol 12-myristate 13-acetate (PMA). Seven different SHE cell pools were tested for sensitivity to NaF promotion following carcinogen treatment. Although the response was heterogeneous, no carcinogen-treated cell pool was refractory to the NaF-induced enhancement. A second fluorocompound, sodium monofluorophosphate (NaMFP), was also found to enhance carcinogen-induced cell transformation in a manner resembling that of NaF.