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This study was conducted to assess the susceptibility of Biomphalaria pfeifferi snails to experimental infection with Schistosoma mansoni for a better understanding of the epidemiology of schistosomiasis in the irrigation schemes in the Sudan. This will help in adopting suitable, efficient and applicable control strategies. Laboratory experiments were carried out on the first generation of non infected Bio. pfeifferi snails collected from four locations; Abu Usher area in Gezira Agricultural Irrigation Scheme (GAIS) and Khartoum State. The parasite strain used was S. mansoni from GAIS. DNA extraction from susceptible and resistant snails from each study location was obtained. Patterns generated by the primer showed clear differences between susceptible and non susceptible snails. The RAPD technique was used to identify susceptible and resistant Bio. pfeifferi snails to S. mansoni infection. The study genetically confirms the presence of resistant (refractory) snails in the country. Further studies are needed in the field of molecular biology to determine the genetic sequences and the genes responsible for resistance before adopting a suitable strategy to control the disease.