The p21(WAF1) gene encodes a cyclin-dependent kinase inhibitor and plays an important role in controlling the cell cycle. Its expression can be induced through wild-type p53-dependent or -independent pathways. Since the p53-dependent pathway is disrupted in more than 50% of human tumors, we wondered whether the p53-independent pathway is also altered during tumor progression. In the present study, we have determined p21(WAF1) induction by mitogenic stimuli, which is known to be a p53-independent process. p21(WAF1) is induced by mitogenic stimuli in all cell lines tested regardless of the status of p53, i.e. wild-type, wild-type inactivated by SV40T or mutant, and the transformation of cells from immortal to tumorigenic and to metastatic. These results indicate that the p53-independent induction of p21(WAF1) pathway is preserved during tumor progression.