SUMMARY Recent work carried out to characterize recessive mutations which render experimental hosts non-permissive to viral infection (loss-of-susceptibility mutants) seems to be converging with new data on natural recessive resistance in crop species, and also with functional analyses of virus avirulence determinants. Perhaps the most well known examples are the studies that identified the eukaryotic translation initiation factors 4E(iso) (eIF(iso)4E) and 4E(eIF4E) as the host factors required for potyvirus multiplication within experimental and natural hosts, respectively, and the potyviral genome-linked protein (VPg) as the viral factor that directly interacts with eIF4E to promote potyvirus multiplication. The purpose of this paper is to review the available information on the characterization of loss-of-susceptibility mutants in experimental hosts, natural recessive resistances and virus avirulence factors, and also to comment on possible implications for the design of new sources of sustainable virus resistance.