Viruses are intercellular pathogens closely integrated within the host's cellular machinery, and chemicals which affect the virus are also harmful to the plant. Therefore, the best way to overcome virus diseases is to breed resistant plants. Traditional breeding procedures allow movement of resistance sources only between closely related species and geneticists lack sufficient sources for their breeding programs. The use of DNA technology to manipulate and move resistance sources against plant pests in general, and viruses in particular, has been widely advocated. This would be in addition to current approaches of inserting viral genes (coat protein, satellite RNA) to obtain resistant plants. For isolation of natural resistance genes the following approaches can be considered: via the gene product, insertional mutation with a transposon or substraction hybridization of mRNA's. As the local lesion response depends on one single dominant gene we thought that it might be suitable for isolation and transformation of plants. We have shown that a host-coded protein, termed "inhibitor of virus replication" (IVR), is induced by virus infection, and inhibits virus replication. IVR has been isolated from protoplast incubation medium and the intercellular spaces of resistant tobacco leaves inoculated with TMV. This protein effectively inhibits the replication of a spectrum of viruses. We have purified and characterized this protein and prepared poly- and monoclonal antisera to IVR. IVR is different from PR-proteins. Immunoprecipitation of translation products of Poly (A)+ RNA from induced resistant tissue yielded a specific product of about 20 K. This Poly (A)+ RNA was used for obtaining cDNA for construction of a library. A clone that reacted positive with IVR antisera produced a protein that inhibited replication of virus.