Co-evolution of wheat and its devastating pathogen Mycosphaerella graminicola (anamorph Septoria tritici), the causal agent of septoria tritici blotch, a foliar disease of wheat, is suggested to occur in Fertile Crescent as their center of origin and, thus, interaction between pathogen virulence and host resistance is important subject to be addressed. We have investigated resistance spectra of 54 wheat genotypes including a set of differentials carrying known resistance genes and virulence patterns of 14 M. graminicola isolates at seedling stage under controlled environmental conditions. The isolates were collected in Iran from five provinces. Diversity in virulence and aggressiveness was observed among the isolates from four provinces. Isolates collected from Golestan province were virulent to all wheat genotypes from germplasm of Iran, while specific resistances were identified to the isolates from other provinces. Among wheat genotypes, cvs. Chamran, Morvarid and Hirmand had the greatest number of specific resistances as well as partial resistance. Wheat genotypes of the differential set also differed in their reactions to the isolates. Arina, Flame and TE 9111 were specifically resistant to the greatest number of isolates from different provinces. Most isolates were virulent to the other differentials such as cvs. Shafir, Estanzuela federal and Courtot indicating that extensive adaption of virulence to most of the known resistance genes (Stb) has occurred in these regions. The new sources of resistance to highly virulent isolates from Iran may also be utilized in wheat breeding programs to develop resistant cultivars against pathogen populations in other countries.