An immune-selection procedure was employed in order to isolate p53-binding sites from rat genomic DNA. One such site was found to reside within the first intron of the cyclin G gene. Cyclin G mRNA levels are strongly elevated upon induction of wild type p53 activity in cells carrying a temperature sensitive p53 mutant. The cyclin G gene also carries a second p53-binding motif upstream to its transcriptional start site. The presence of two high affinity p53-binding sites may confer upon the cyclin G gene the potential to be activated very efficiently by p53. These data raise the possibility that cyclin G may be a downstream mediator of at least some of the biological effects of p53.