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BACKGROUND: Schistosomiasis is one of the chronic and neglected tropical diseases affecting ruralcommunities. Heavy infections contribute to anemia and can retard children's growth, physical activityand cognitive function. This study was conducted in order to determine the prevalence, intensity andvariation of Schistosoma mansoni infection among human subjects in geographically apart localities.The prevalence and intensity of Schistosoma mansoni infection was assessed in three geographicallyapart endemic areas of Ethiopia from May to August 2010 through cross-sectional approach.METHODS: A total of 1073 individuals (528 males and 545 females) were found eligible for the study.Their age ranged from 5-60 years with mean age of 11 years in Wondo Genet, 22 years in Kemissie and24 years in Sille-Elgo. Small plastic sheets were distributed to the study participants and sizable stoolspecimens were collected and examined using Kato-Katz method (41.7mg template).RESULT: The prevalence of Schistosoma mansoni infection among the study participants in Kemissie,Wondo Genet and Sille-Elgo was 89.6%, 59.9%, and 31.6%, respectively. The highest geometric mean ofegg per gram of stool for Kemissie, Wondo Genet and Sille-Elgo was, 5208 and 346, 8472 and 252, 3960and 91, respectively.CONCLUSION: It was observed that there was comparable variation in the prevalence and intensity ofinfection among the study localities. Moreover, it is indicated that S. mansoni is still an ongoing publichealth problem which requires integrated intervention activities in the country.