THE cellular phosphoprotein p53 inhibits progression through the mammalian cell cycle^1,2. Both p53 alleles are frequently mutated in human tumours^3,4, indicating that p53 is a tumour suppressor. Recent studies have suggested that p53 functions as a transcrip-tional activator5–8, but the significance of this activity in cell-cycle control has not been established. The adenovirus 2 (Ad2) early IB (E1B) 55K protein binds to p53 in transformed cells⁹ and contributes to oncogenic transformation by Ad2 (refs 10-12). Here we report that mutants of E1B 55K and wild-type Adl2 E1B 54K proteins show a strong correlation between their ability to inhibit p53-mediated transcriptional activation and their ability to cooperate with adenovirus El A protein in the transformation of primary cells. These results indicate that p53 probably inhibits cell cycling by functioning as a transcription factor.