The p73 proteins alpha and beta were identified based on their similarity to the tumour suppressor gene product p53. p53 and the p73 proteins activate transcription from p53-responsive promoters. The large T antigen of simian virus 40 (SV40) forms a specific complex with p53 and inhibits p53-mediated transcription. Here we show that the large T antigens from SV40 and JC virus strongly reduce the transcriptional activity of p53 but do not detectably affect the ability of the p73 proteins to transactivate. p53 but not the p73 proteins associate with SV40 T antigen in vitro. Finally, p53 colocalizes with a cytoplasmic mutant of SV40 T antigen, whereas both variants of p73 fail to colocalize with cytoplasmic T antigen. These results indicate that T antigen selectively binds and inactivates p53 but does not detectably affect the p73 proteins.