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Tobacco plants transformed with the RNA polymerase (RdRp) gene of potato virus X (PVX) that are extremely resistant to infection by potato virus X have previously been described. The PVX‐resistant plants accumulated the RdRp protein at a lower level than fully susceptible plants transformed with the same RdRp construct. In this paper the difference between the PVX‐resistant and susceptible transformed plants is investigated and it is demonstrated that there are three associated phenotypes of the RdRp transgene that vary in parallel between transformed lines. These phenotypes are: accumulation of the transgenic RdRp RNA at a low level; strain‐specific resistance to PVX; and the ability of the transgene to trans‐inactivate homologous transgenes. This gene‐silencing potential of the transgenes conferring PVX resistance was illustrated by analysis of progeny from a cross between a transformant that was extremely resistant to PVX and a second PVX‐susceptible transformant. In other transformants, in which the resistance was less extreme, the same three phenotypes were associated but in a transgene dosage‐dependent manner. The same association of strain‐specific resistance and low‐level accumulation of the transgenic RdRp RNA was observed with plants that were transformed with mutant or wild‐type versions of the RdRp gene. Strain‐specific resistance was also produced in plants transformed with untranslatable versions of the RdRp transgene. Based on these data it is proposed that homology‐dependent gene silencing and transgenic resistance to PVX may be due to the same RNA‐based mechanism. An undefined genomic feature is proposed to account for the variation in the resistance and trans‐inactivation phenotypes of different transformants. It is further proposed that this genome feature influences a cytoplasmic mechanism that degrades RNA with sequence homology to the silencing transgene.

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