Transfection of the v-Ki-ras oncogene into rat-1 fibroblasts resulted in the establishment of cell lines that were transformed, tumorigenic, and sensitive to lysis by natural killer (NK) cells. Characterization of effectors indicated that the killing was not related to Lyt-1+ or Lyt-2+ cells (T cells) but was associated with cells bearing NK markers (asialo GM1, NK-1.2+, and NK-2.1+). Transfected targets were also killed by cloned NK lines. The transformation determinants on rat-1 transfectants cross-competed with YAC 1.2 lymphoma cells, suggesting a common target structure on these two diverse cell types. The results indicate that the NK surveillance system can recognize and kill cells newly transformed by a member of the ras oncogene family.