To determine the contribution of~ 53 loss to tumor progression, we have induced abnormal proliferation In the brain choroid plexus epithelium of transgenic mice using a SV40 T antigen fragment that perturbs pRB family function but does not affect~ 53 function. Tumors induced by this mutant develop slowly compared with those Induced by wild-type T antigen. Suppressed tumor growth Is directly attributable to~ 53 function, since rapid tumor development occurs when the T antigen fragment Is expressed In p53-null mice. In p53-heterozygous mice, stochastic loss of the wildtype~ 53 allele results in the focal emergence of aggressive tumor nodules characteristic of tumor progression. In each case, aggressive tumor development in the absence of~ 53 function corresponds to a decrease in the level of apoptosis. These results provide in vivo evidence that p53-dependent apoptosls, occurring In response to oncogenlc events, Is a critical regulator of tumorigenesis.