Non-host resistance is investigated as a potential source of durable resistance. However, the genetics of non-host resistance between closely related plant species and their corresponding pathogens would indicate that in these interactions, non-host resistance primarily involves major genes that operate on a gene-for-gene principal similar to that seen in host resistance. Wheat is a non-host of the barley-attacking form of the fungus responsible for yellow rust, i.e. Puccinia striiformis f. sp. hordei. While P. striiformis f. sp. hordei is generally unable to infect wheat, a partial susceptibility was exhibited by the wheat variety Chinese 166. Consequently, in the cross Lemhi x Chinese 166 two major QTLs for resistance to P. striiformis f. sp. hordei were identified: one on chromosome 1D and a second on 2B. These two QTLs accounted for 43.5% and 33.2% of the phenotypic variance for resistance to barley yellow rust, respectively. In addition, two QTLs of smaller effect were also identified: one on chromosome 5A, contributing 5.1% of the variance and a second on chromosome 6A, contributing 10.9% to the phenotype. The QTL on 6A was derived from the susceptible variety, Chinese 166. In all cases the resistance towards P. striiformis f. sp. hordei was associated with a visual chlorosis/necrosis response typical of race-specific host resistance.