Full length cDNAs for p53 were made by reverse transcription-polymerase chain reaction of total RNA from two normal woodchuck livers. Two randomly chosen clones from each liver were sequenced and shown to be identical. This sequence revealed 80% or more identity with p53 sequences from human, monkey, and mouse. The cDNA was translated into a ∼55 kD protein in vitro that was immunoprecipitated by antibodies to p53. Cotranslation of woodchuck p53 with woodchuck hepatitis virus X antigen, followed by immunoprecipitation suggested X/p53 complex formation. Similar complexes were also immunoprecipitated from extracts of infected liver, but not from uninfected liver. The finding of X/p53 complexes in vivo and in vitro in the woodchuck hepadnavirus system, combined with analogous data with hepatitis B, suggests a common mechanism by which these viruses contribute to hepatocellular transformation.