Abstract: In the present study, we assessed the pathogenicity of the prevalent strains of Rice Yellow Mottle Virus (RYMV) present in Eastern Uganda and identified suitable donors for durable resistance among rice cultivars. Screenhouse studies were conducted using eight isolates of the virus against 16 rice cultivars. Isolate aggressiveness and cultivar resistance were assessed in terms of disease severity and percentage stunting following mechanical inoculation by the finger-rub technique. Highly significant differences (p<0.001) between rice cultivars for both parameters revealed the occurrence of different genetic factors for resistance among the rice cultivars. Mean disease severity and percentage stunting ranged between 0.9-9.0 and -1.1-32.4%, respectively for individual cultivars. The absence of significant isolate-by-cultivar interaction suggests a race-non-specific resistance. No significant differences in aggressiveness were obtained between isolates, indicating limited pathotype diversity in Eastern Uganda as evidenced by the absence of mega-environments among the prevalent strains. Based on cultivar resistance ranking, three O. sativa subspecies japonica (NERICA6, ITA257 and ITA325) and two O. sativa subspecies indica (WAC116 and WAC117) were identified as the potential sources of resistance for improving susceptible local varieties. The confirmed resistance breakdown in GIGANTE has important implications for plant breeding and disease control strategies. Therefore, pyramiding different sources of resistance is recommended for enhanced durability of resistance. In addition, the use of sufficient prerelease challenge by the combination of isolates with different levels of aggressiveness will delay the rise of susceptibility in deployed resistant cultivars.