We have investigated a mutation in the p53 gene leading to expression of a truncated 46,000-dalton protein in a Friend virus-induced erythroleukemia cell line. cDNA sequence analysis revealed a deletion of nucleotide sequences in exon 7 and part of exon 8; 17 additional nucleotides, derived from intron 6, were present in the cDNA and served to maintain the reading frame of the encoded protein. Comparison with p53 protein from other species indicated that the region of the molecule missing in p46 included a highly conserved region. In addition, p46 failed to bind SV40 large T antigen in vitro under conditions which promoted binding of p53 to large T. It seems likely, therefore, that an important functional property of p53 may be affected by the mutation.