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Nitrate contamination of shallow aquifers poses a major challenge in the development of sustainable agriculture, particularly in (semi-) arid regions, where groundwater is also used as potable water. In this study we estimate the relative contribution of the various nitrate sources contaminating the shallow aquifers underlying agricultural fields in the extremely arid region of the Central Arava Valley (CAV), southern Israel. The estimates are based on a chemical and isotopic mixing-reaction model describing the evolution of the delta(18)O(NO)3 and delta N-15(NO3) isotopic compositions from the sources to the aquifer. The model indicates that all fertilizers used in the agricultural fields: synthetic NO3-, synthetic NH4+ and manure, contaminate the CAV groundwater with nitrate. In most of CAV groundwaters, the contribution of each fertilizer to the groundwater contamination is relative to its proportion in the fertilization scheme of the cultivated fields. Two exceptions of this general observation were found: 1. One field showed a direct nitrate contamination from a "leaking" sewage reservoir, as indicated by its exceptionally high delta N-15(NO3) value that reached 9.2%; and 2. A very shallow alluvial aquifer, recharged by winter floods and not by the irrigation water, showed no nitrate isotopic "fingerprint" of manure, which is applied to the cultivated fields only during summer. Groundwater nitrate contamination is actuated by infiltration of irrigation water, which in addition underwent salinization as a result of evapotranspiration in the cultivated fields. Based on the relatively uniform and depleted groundwater delta O-18(H2O) compositions and the depleted delta O-18(NO3) values, within the possible range of fertilizers-derived nitrate as deduced by the model, the water-loss in the cultivated fields is transpiration-controlled. The isotope mixing-reaction model used here to identify the major nitrate contamination sources maybe used to help design a sustainable cultivation management strategy in similar arid regions. It can also be used to assess the fertilization efficiency and the relative impact of each fertilizer type. Such models may be particularly useful in evaluating highly heterogeneous and complicated aquifer systems, for which the formulation of absolute water and nitrate mass balances are impossible. (C) 2015 Elsevier Ltd. All rights reserved.