In the present study we characterized the responses of the cell line HST-alpha, stably transformed by a secreted form of human fibroblast growth factor-1 (acidic FGF) gene, and its parental NIH 3T3 cell line to recombinant murine (rMu) TNF-alpha. Treatment of HST-alpha cells with rMu TNF-alpha can significantly reduce the number of foci formed in the in vitro transformation assay. In the presence of the RNA polymerase inhibitor actinomycin-D, the transformed HST-alpha cell is more susceptible to the cytotoxicity of rMu TNF-alpha than is its parental NIH 3T3 cell. The median lethal concentrations (LC50) of rMu TNF-alpha to HST-alpha cell and NIH 3T3 cell were 0.35 ng/ml and 4.56 ng/ml respectively. These results demonstrated that the introduction of a single oncogene or a growth factor gene to a cell can change the cell's response to cytokines.