Different potato genotypes expressing extreme resistance to potato virus X were inoculated with potato virus X strains cp, CP4, and HB and with three PVX mutants constructed in vitro. Using these viral strains and mutants, the involvement of the coat protein, specifically the single amino acid residue at position 121 within this protein, in the resistance-breaking capacity of strain HB was confirmed for all resistance genes tested. We concluded that the extreme resistance expressed in Solanum x chaucha, S. x curtilobum, S. x juzepczukii, and S. vernei is conferred by Rx genes (Rx(cha), Rx(cur), Rx(juz), and Rx(vrn), respectively) that employ the same mechanism of interaction with the PVX coat protein as Rx, Rx(acl), and RX(adg). Although S. sucrense clone OCH 11926.4 was resistant to both common PVX strains and PVX(HB), it was susceptible to the mutant isolates. We hypothesized that at least two viral determinants, one of which is not located in the coat protein coding region, interact with the S. sucrense resistance gene.