Xenotransplantation may develop into a medical technology able to save or improve the quality of life. Porcine endogenous retroviruses (PERVs), because they are integrated in the genome of all pig strains, because they are produced by normal pig cells, and because they can infect human cell in vitro, are considered to be the main microbiological risk if pig cells, tissues or organs are to be transplanted. Indeed, serial passaging of PERV on human cells, simulating the situation during xenotransplantation, was found to increase the titer of the virus and was associated with corresponding genetic changes in the viral LTR. In vitro infection studies showed a productive infection of primary cells of different species including non-human primates and man. However, using newly developed sensitive detection methods, evidence for PERV transmission was seen neither in over 200 patients who had received porcine xenotransplants nor in butchers frequently exposed to pig tissues. Similarly, rats, guinea pigs, minks, rhesus macaques, pig tailed macaques and baboons inoculated with high doses of PERV and given strong daily immunosuppressive treatment failed to exhibit evidence of infection. These data are crucial for the evaluation of xenotransplantation safety because they demonstrate that PERVs cannot easily be transmitted to other species including man.