Two non-tumorigenic variant cells were isolated from UV-irradiated Balb/c 3T3 cells on the basis of their different responsiveness in phorbol ester-induced morphological change (rounding formation). They showed marked differences of lung metastatic potentials after intravenous injections of their v-src transformants into nude mice; phorbol ester-resistant variant TR4 cells transformed by v-src were hypermetastatic, whereas v-src transformants of phorbol ester-sensitive variant TR5 cells were not metastatic at all. These different metastatic responses were not observed in v-K-ras-induced transformants of the variants. These non-tumorigenic variant cells may pre-acquire the genetic alteration of certain src-specific and metastasis-associated factors. This system may be useful for genetic analysis of the induction of metastasis.