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Karst springs of the Zagros Mountains contribute a significant amount to agricultural and human water demands of western and south-western Iran. For an adequate management of available water resources in semi-arid and arid regions, sufficient hydrological monitoring is needed, and hydro-chemical and isotope hydrological data provide important additional information. About 350 water samples were collected from precipitation, river water, and karst springs of the upper part of the Karkheh River Basin (20,895km(2)) located between 33 degrees 35(’) and 34 degrees 55(’) North and 46 degrees 22(’) and 49 degrees 10(’) East with elevations ranging from 928 to 3563m above sea level. Sampling was conducted in monthly time resolution from August 2011 to July 2012. All samples were analysed for hydro-chemical parameters (pH, electrical conductivity, and major ions) and stable isotopes (deuterium, oxygen-18). Isotope values of precipitation indicate a local meteoric water line (Zagros MWL delta H-2=6.8 delta O-18+10.1; R-2=0.99) situated between the Mediterranean MWL and Global MWL. Spring and river water isotope values vary between-7.1 and-4.1 parts per thousand, and-38 and-25 parts per thousand for delta O-18 and delta H-2, respectively, responding to winter snowmelt and evaporation. This work implements stable isotopes and hydro-chemical information of springs and river water to understand hydrological and hydro-geological interrelations in karstic semi-arid areas and helps to improve the current water resources management practices of western Iran.