Viruses can exchange genetic material when at least two different viral genomes co-infect the same host cell. Progeny can then become hybrid through different mechanisms, such as reassortment of segments when the parental genomes are fragmented [10] , intra-molecular recombination when polymerases switch templates (in RNA viruses) [11] , or homologous or non-homologous recombination (in both RNA and DNA viruses). Quantification of viral recombination in multicellular organisms has been attempted under two distinct experimental approaches: in vitro (in cell cultures) [12, 13, 14, 15] , and in vivo (in live hosts) [16, 17, 18] . The in vitro approach, which has so far been applied only to animal viruses, allows the establishment of the ''intrinsic'' recombination rate in experimentally co-infected cells in cell cultures [14, 15, 19] . However, it does not necessarily reflect the situation in entire, living hosts, where the frequency of coinfected cells is poorly known and depends on many factors such as the size of the pathogen population, the relative frequency and distribution of the different variants, and host defense mechanisms preventing secondary infection of cells. The in vivo experimental approach is closer to biological conditions and may thus be more informative of what actually happens in ''the real world.'' However, as discussed below, numerous experimental constraints have so far precluded an actual quantification of the baseline rate of recombination. First, many experimental designs have used extreme positive selection, where only recombinant genomes were viable (e.g., [13, 20, 21] ). Other studies did not use complementation techniques but detected recombinants by PCR within infected hosts or tissues [18, 22, 23, 24, 25] , which provides information on their presence but not on their frequency in the viral population. So far, no quantitative PCR or other quantitative method has been applied to evaluate the number of recombinants appearing in an experimentally infected live host. Finally, recent methods based on sequence analysis inferred the population recombination rate, rather than the individual recombination rate [1, 26, 27] . While results from these methods certainly take in vivo recombination into account, there are other caveats: isolates have often been collected in different hosts-sometimes in different geographical regions-and sometimes the selective neutrality of sequence variation on which these estimates are based is not clearly established. Estimates from such studies by essence address the estimation of the recombination rate at a different evolutionary scale.