Post-lactational involution of the mammary glandprovides a system in which to study the expression andfunction of genes that regulate apoptosis in the contextof a normal tissue. The functions of the p53 tumor suppressor gene have been extensivelystudied as a mediator of apoptosis in response to DNAdamage, but its regulation in normal physiologicprocesses has been poorly characterized. Expression of p53 mRNA was shown to be among the firstgenes to be induced in mammary tissue following weaningof neonates. Although involution proceeds in the absenceof a functional p53 gene, it is delayed compared to normal individuals. Therefore, involutioncan be viewed as biphasic with initial responses beingsensitive to p53, whereas secondary responses beingp53-independent. These observations can be exploited to determine the subset of genes that arep53-responsive and that mediate the effects of p53 innormal mammary tissue.