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Wheat head blast (WHB), caused by the fungus Magnaporthe oryzae pathotype triticum , is a devastating disease affecting South America and South Asia. Despite 30 years of intensive effort, the 2N V S translocation from Aegilops ventricosa contains the only useful source of resistance to WHB effective against M. oryzae triticum isolates. The objective of this study was to identify non-2N V S sources of resistance to WHB among elite cultivars, breeding lines, landraces, and wild-relative accessions. Over 780 accessions were evaluated under field and greenhouse conditions in Bolivia, greenhouse conditions in Brazil, and at two biosafety level-3 laboratories in the United States. The M. oryzae triticum isolates B-71 (2012), 008 (2015), and 16MoT001 (2016) were used for controlled experiments, while isolate 008 was used for field experiments. Resistant and susceptible checks were included in all experiments. Under field conditions, susceptible spreaders were inoculated at the tillering stage to guarantee sufficient inoculum. Disease incidence and severity were evaluated as the average rating for each 1-m-row plot. Under controlled conditions, heads were inoculated after full emergence and individually rated for percentage of diseased spikelets. The diagnostic marker Ventriup-LN2 was used to test for the presence of the 2N V S translocation. Four non-2N V S spring wheat International Maize and Wheat Improvement Center breeding lines (CM22, CM49, CM52, and CM61) and four wheat wild-relatives ( A. tauschii TA10142, TA1624, TA1667, and TA10140) were identified as resistant (<5% of severity) or moderately resistant (5 to <25% severity) to WHB. Experiments conducted at the seedling stage showed little correlation with disease severity at the head stage. M. oryzae triticum isolate 16MoT001 was significantly more aggressive against 2N V S-based varieties. The low frequency of WHB resistance and the increase in aggressiveness of newer M. oryzae triticum isolates highlight the threat that the disease poses to wheat production worldwide and the urgent need to identify and characterize new resistance genes that can be used in breeding for durably resistant varieties.