<jats:title>ABSTRACT</jats:title> <jats:p> Specific-pathogen-free (SPF) swine appear to be the most appropriate candidate for pig to human xenotransplantation. Still, the risk of endogenous retrovirus transmission represents a major obstacle, since two human-tropic porcine endogenous retroviruses (PERVs) had been characterized in vitro (P. Le Tissier, J. P. Stoye, Y. Takeuchi, C. Patience, and R. A. Weiss, Nature 389:681–682, 1997). Here we addressed the question of PERV distribution in a French Large White SPF pig herd in vivo. First, PCR screening for previously described PERV envelope genes <jats:italic>envA</jats:italic> , <jats:italic>envB</jats:italic> , and <jats:italic>envC</jats:italic> (D. E. Akiyoshi, M. Denaro, H. Zhu, J. L. Greenstein, P. Banerjee, and J. A. Fishman, J. Virol. 72:4503–4507, 1998; Le Tissier et al., op. cit.). demonstrated ubiquity of <jats:italic>envA</jats:italic> and <jats:italic>envB</jats:italic> sequences, whereas <jats:italic>envC</jats:italic> genes were absent in some animals. On this basis, selective out-breeding of pigs of remote origin might be a means to reduce proviral load in organ donors. Second, we investigated PERV genome carriage in <jats:italic>envC</jats:italic> negative swine. Eleven distinct full-length PERV transcripts were isolated. The sequence of the complete envelope open reading frame was determined. The deduced amino acid sequences revealed the existence of four clones with functional and five clones with defective PERV PK-15 A- and B-like envelope sequences. The occurrence of easily detectable levels of PERV variants in different pig tissues in vivo heightens the need to assess PERV transmission in xenotransplantation animal models. </jats:p>