Technical Abstract: Tan spot, caused by Pyrenophora tritici-repentis (Ptr), is an economically important foliar disease in the major wheat growing areas of the world. Multiple races of the pathogen have been characterized based on their ability to cause necrosis and/or chlorosis on differential wheat lines. Isolates of race 5 cause chlorosis only, and they produce a host-selective toxin designated Ptr ToxB that induces chlorosis when infiltrated into sensitive genotypes. The ITMI mapping population was used to identify genomic regions harboring QTLs for resistance to fungal inoculations of Ptr race 5 and to determine the chromosomal location of the gene conditioning sensitivity to Ptr ToxB. The toxin-sensitivity gene, which we are designating Tsc2, mapped to the distal tip of the short arm of chromosome 2B. This gene was responsible for the effects of a major QTL associated with resistance to the race 5 fungus and accounted for 69 percent of the phenotypic variation. Additional minor QTLs were identified on the short arm of 2A, the long arm of 4A, and elsewhere on chromosome 2B. A multiple regression model consisting of the major QTL on 2BS identified by the toxin insensitivity gene, a marker underlying a minor QTL on 2BS, a marker on 4AL, and an epistatic interaction accounted for 76 percent of the total phenotypic variation for resistance to Ptr race 5. The results of this research indicate that Ptr ToxB is a major virulence factor, and the markers underlying significant QTLs should be useful for introgression of resistance into adapted germplasm.