p73, a recently identified gene highly homologous to p53, can transactivate p53 target genes and induce apoptosis. Here we report the identification of an NH(2)-terminal truncated isoform of human p73, DeltaNp73, which is capable of suppressing p53- and p73-dependent transactivation. We speculate that this suppression is achieved by competing for the DNA binding site in the case of p53 and by direct association in the case of TAp73. Expression of DeltaNp73 in cancer cell lines also inhibited suppressive activity of p53 and TAp73 in colony formation, implying possible involvement of DeltaNp73 in oncogenesis by inhibiting the tumor-suppressive function of p53 and TAp73. Also reported is the identification of TAp73eta, a new member of the COOH-terminal truncated isoform of p73 and tissue-specific expression of these isoforms, along with other previously identified p73 isoforms.