Transgenic resistance to tomato spot wilt virus (TSWV) has been accomplished by expressing the viral nucleocapsid (N) protein gene in transgenic tobacco. Similar levels of protection, i.e., complete immunity to the virus in homozygous S2 plants, have been observed when an untranslatable N protein gene was expressed, indicating that the N protein gene-based resistance is mediated by the expressed transgene viral RNA. To test whether this RNA-mediated resistance is limited to plants that express viral N protein RNA sequences, 325 transgenic plant lines were produced that expressed a wide range of parts of the TSWV RNA-genome or its complement, spanning over 70␘f the TSWV genome, including the entire S and M RNA sequences. The progenies of these plants were screened for resistance to TSWV. Remarkably, only plants that expressed N or NSm gene sequences displayed immunity to the virus. The functions of these proteins may be blocked early in the infection process, suggesting an important role for these proteins in early stages of systemic virus infection. The mechanism by which the expression of transgenic RNAs can cause immunity in transformed plants is discussed.