Human skin fibroblasts are extremely refractory to neoplastic transformation by ionizing radiation [C. Borek, Nature 283, 776-778 (1980); M. Namba, H. Nishitani, and T. Kimoto, J. Exp. Med. 48, 303-311 (1978)] and are therefore unsuitable for quantitative studies of dose-effect relationships. We show here that a nontumorigenic human hybrid cell line (HeLa X skin fibroblast) can be neoplastically transformed by treatment with gamma radiation. Furthermore, a dose-response relationship has been established. We propose that this human hybrid cell line may be a useful system for mechanistic studies of transformation from the preneoplastic to the neoplastic state by ionizing radiation and other agents.