In the light of the evidence and discussion presented during The Royal Society Discussion Meeting it seems to me that the oral polio vaccine (OPV) hypothesis for the origins of human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome epidemic is less tenable now than one year earlier. The OPV hypothesis does not accord with HIV phylogenetic studies: the geographical correlation has been challenged; the testimony of those directly involved with OPV trial vaccines denies the use of chimpanzees, corroborating tests on the still–available vials of the CHAT vaccines, which contain neither simian immunodeficiency virus nor chimpanzee DNA. Yet one lesson to be learned from considering OPV as a source of HIV is how plausibly it might have happened and how cautious we need to be over introducing medical treatments derived from animal tissues, such as live, attenuated vaccines or xenotransplantation. To cast doubt on the OPV hypothesis is not to dismiss entirely the role of iatrogenic factors in HIV transmission from chimpanzees in the first instance, in HIV adaptation to onward transmission during its early phase in humans, or in the later spread of HIV to patients, for example, with haemophilia. To reduce the argument over the origins of HIV to the ‘OPV hypothesis’ versus the ‘cut–hunter hypothesis’ is an oversimplistic and false antithesis. Both natural and iatrogenic transmission of many retroviruses, including HIV, have been thoroughly documented and are not mutually exclusive. Exactly how, when and where the first human(s) became infected with the progenitor of HIV–1 group M, which gave rise to the pandemic strain, is likely, however, to remain a matter of conjecture.