ABSTRACT The International Maize and Wheat Improvement Center (CIMMYT), Mexico, germplasm-derived wheat (Triticum aestivum) Kavkaz-K4500 L.6.A.4 (KK) is one of the major sources of resistance to Septoria tritici blotch (STB). KK is resistant to STB in field conditions in the UK even though a large majority of Mycosphaerella graminicola isolates are virulent to it. The genetics of the resistance of KK to four isolates of M. graminicola were investigated. KK has at least five isolate-specific resistance genes including Stb6 on chromosome 3A plus a second gene for resistance to isolate IPO323, two genes on chromosome 4A, both in the region where Stb7 is located with one designated as Stb12, and a gene designated Stb10 on chromosome 1D. Taken together, the widespread use of KK as a source of resistance to STB, its high resistance in field conditions, and its high susceptibility to M. graminicola isolates, which are virulent to all its resistance genes, suggest that high levels of field resistance to STB might be achieved by pyramiding several isolate-specific resistance genes.