Septoria tritici blotch (STB) disease is one of the most important diseases of wheat in North America, China, and particularly in Europe. STB has been developed by cultivating Mexican wheat cultivars in Iran since 1966. The disease is caused by hemibiotrophic fungus, Zymoseptoria tritici , resulting in up to 50 percent of yield losses under favorable conditions. The disease symptom of infection by Z. tritici is necrotic red-brown to pale brown spot with black, small, and scattered pycnidium. Iran is located in Fertile Crescent, a region where both hexaploid bread wheat and Z. tritici are most likely originated. This study was conducted to address wheat- Z. tritici interactions by using phenotypic and molecular approaches. To this aim, each samples were collected from infected wheat fields across the counry of and were subjected to Z. tritici isolations. In total, 85 Z. tritici samples were isolated, from which 38 isolates were tested on 23 wheat differentials. Among wheat differentials, 3HD-138, M3 synthetic, Flame, Kavkaz-K4, and Km41 cultivars showed the highest level of resistance to Irania Z. tritici isolates. In addition, the presence of the Stb6 gene was evaluated in hexaploid bread wheat and its wild relatives using specific primers (Ha3-WF1/Ha3-WR1) that could amplify a 568 bp band. The presence ofthe Stb6 gene was confirmed in differential cultivars previously known to possess the Stb6 gene. Stb6 was detected in some Iranian wheat commercial cultivars while the frequency of this gene in wheat wild relatives was very low. Moreover, the presence ofthe AvrStb6 gene was examined in Iranian isolates of Z. tritici using specific primers (Avr6-ztF1/Avr6-ztR1) amplifying a 362 bp band. The PCR data showed that the frequency of the AvrStb6 gene was very low in Iranian Z. tritici populations. Overall, phenotypic data showed that no significant correlation was presented between the pathogenic profile and geographical locations. Furthermore, the low frequency of AvrStb6 indicates that other unknown effectors other than AvrStb6 are most likely presented in Iranian Z. tritici populations that their identification is of interest. Key words : Zymoseptoria tritici , Stb6 , AvrStb6 , plant-microbe interactions.