Two important sources of Capsicum annuum (bell pepper) resistance were evaluated for their response to inoculation with two isolates of Tobacco etch virus strain NW (TEV-NW, genus Potyvirus). The resistant cultivars were CA4 and Dempsey, which contain the pvr1 and pvr12 resistance genes, respectively. TEV-NW was maintained by mechanical passage in the susceptible pepper cultivar Early Calwonder and Nicotiana tabacum cv. Kentucky 14. In initial experiments, the TEV-NW isolate maintained in Early Calwonder infected two of seven CA4 plants; however, none of the CA4 plants inoculated with the TEV-NW isolate maintained in Kentucky 14 were infected. The infected CA4 plants had low virus titres in non-inoculated leaves and did not develop visible symptoms. When the infected CA4 plants were used as inoculum of additional CA4 plants, all newly inoculated plants became infected, developed systemic symptoms and accumulated virus in non-inoculated leaves more quickly than the originally infected CA4 plants. This new NW isolate, referred to as NW-CA4, was shown to overcome the resistances expressed by both CA4 (pvr1) and Dempsey (pvr12). The potyviral VPg is believed to be the determinant for pvr1 and pvr12 resistance genes, both of which are eIF4E-encoding genes. The VPg amino acid sequence for NW-CA4 was determined and compared with that of NW isolates and different TEV strains. No amino acid variation was identified that explained the infectivity of NW-CA4 in CA4 and Dempsey plants.