The disease caused by rice yellow mottle virus (RYMV) is a serious problem for African rice growers in large-scale irrigated programs. As there are very few suitable natural sources of RYMV resistance, we have investigated a transgenic approach using widely grown, RYMV-susceptible cultivars of rice and a transgene encoding the RNA-dependent RNA polymerase of RYMV. Transformed lines were resistant to RYMV strains from different African locations. In the most extreme examples there was complete suppression of virus multiplication. Resistance was stable over at least three generations. Subject to satisfactory field testing, these transgenic lines may be suitable for introduction into RYMV-affected rice-growing areas. In the most resistant line, transcription analysis indicated that the resistance derives from an RNA-based mechanism associated with posttranscriptional gene silencing.