SUMMARYThe unique periodic nature of equine infectious anaemia (EIA) is believed to result from the ability of the infecting virus, EIAV, to undergo relatively rapid antigenic variations which circumvent host immune responses resulting in distinct virus populations in sequential clinical episodes in the persistently infected horse. This model was examined by oligonucleotide mapping comparisons of the RNA genomes of selected isolates of EIAV. Variations in oligonucleotide maps could be reproducibly demonstrated (i) after adaptation of the laboratory strain of EIAV to replication in a pony, (ii) after serial passage of virus between two ponies, and (iii) after a prolonged persistent infection in a single pony. In the latter case, the two isolates examined were recovered from different clinical episodes and were shown to be antigenic variants. In contrast, no variations in RNA structure could be detected in oligonucleotide maps of virus isolated after prolonged passage in tissue culture. Thus, these results support our concept that EIAV is a highly mutable virus, which may give rise to antigenic variants in the presence of immune pressures. The degree of variation observed between oligonucleotide maps is similar to that observed previously between variants of visna virus. These similarities between EIAV and visna virus suggest that genomic point mutations producing antigenic variants may be a more important mechanism of retrovirus persistence than was previously recognized.