Two lung and two colon carcinoma cell lines of human origin, which contained the same activated rasK transforming gene, expressed abnormal species of p21 that were distinct from the p21 proteins expressed in normal human cells and other human carcinomas. The abnormal species of p21 expressed by three of these cell lines were indistinguishable from each other, but differed from the abnormal p21 expressed by one lung carcinoma cell line. NIH cells transformed by DNAs of these carcinomas expressed the same abnormal p21 species, indicating that these abnormal proteins were encoded by the activated rasK genes detected by transfection. These results indicate that transforming activity of rasK genes in human lung and colon carcinoma cell lines is activated by mutations which alter the structure of their gene products, and that activation of rasK genes can result from different molecular alterations in different individual neoplasms.