Finally, we demonstrated that rhinovirus evolves by recombination in its natural host. Known to be a driving force of enterovirus evolution, rhinovirus recombination among clinical strains has never been observed. Two clinical isolates of 40 viruses analyzed resulted from recombination events and their breakpoints were identifi ed within the 5′-UTR sequence and the N terminus of protein 3C, respectively. These fi ndings are consistent with the fact that recombination breakpoints in picornaviruses are restricted to nonstructural regions of the genome or between the 5′-UTR and the capsid-encoding region (40) . Our observations provide new insight on the diversity and ability of rhinovirus to evolve in its natural host. The fact that only 2 of 40 analyzed viruses over a 9-year period were recombinants is suggestive of a lower recombination frequency in rhinoviruses than in other picornaviruses (32, 40) and might be related, but not exclusively, to the short duration of rhinovirus infection (18, 31, 32) . Recombination events occurred between HRV-A genotypes, but whether they can occur in species B and C remains unknown. Interspecies recombination is rare in picornaviruses and is mainly the result of in vitro experiments. For rhinoviruses, the different location of cre elements in each species might be an additional limiting constraint (17) .