To clarify the correlation between metabolic stabilization of p53 protein and cellular transformation, we transformed the normal rat cell line F2408 with various viral transforming genes and examined the expression and stability of p53 protein in these transformed cells by pulse-chase immunoprecipitation experiments. As expected, the level of p53 in the SV40-transformed rat cell line was higher than that in the normal cell line and its stability was also increased. In contrast, in cells transformed with the E7 and E6 genes of human papillomavirus type 16, the level and stability of p53 were similar to those in the normal cells. In cells transformed by the middle T or large T of polyomavirus, v-K-ras, and v-src, the levels and stabilities of p53 were also not elevated, although the level of p53 was increased in activated c-H-ras-transformed cells without an increase in its stability. These results show that increased stability and expression of the p53 protein are not common events in viral transformation of the rat cell line. In addition, we demonstrated with a monoclonal antibody specific for the mutant form of p53 that cellular transformation by viral transforming genes does not involve mutational activation of p53 to a oncogenic form.