The expression of translatable sequences of either one of the two Andean potato mottle virus (APMoV) coat protein (CP) genes (CP22 and CP42) and of the nontranslatable sequence of CP42 in transgenic tobacco provided protection against APMoV. Resistance was mediated by CP transgene RNAs rather than the protein, as an inverse correlation between resistance and the accumulation levels of CPs transgene mRNAs was observed. These data indicated that a post-transcriptional gene silencing (PTGS) mechanism is likely involved in the APMoV CP RNA-mediated protection. Moreover, the HindIII-AccI restriction pattern of the CP22 transgene was different in susceptible and resistant transgenic plants, suggesting the involvement of methylation in PTGS. Southern blot experiments also revealed that CPs transgene insertion loci and organisation in the plant genome may play a role in determining the degree of protection.