Abstract: The objective of this study was to evaluate and map regional patterns of heavy metals (Cu, Cd, Ni and Zn) occurrence in south of Iran. The study was performed in Shush and Andimeshk plains in the south part of Iran, with high agricultural activities that cover an area of 1100 km2 between the Dez and Karkhe rivers. This region was divided into four sub-regions A, B, C and D. Additionally 168 groundwater samples were collected from 42 water wells during the months April, May, August and September of 2004. The Flame Atomic Absorption Spectrometry (AAS-Flame) was used to measure the heavy metals concentration in water samples. The results demonstrated that all of the samples, Cu, Zn and Ni concentrations have been shown below the EPA MCLG, EPA secondary standard and EPA MCL, respectively, but Cd, contents of 4.8% of all samples was higher than EPA MCL. The heavy metals concentration is more pronounced in south part than northern part of the studied area. Absent confining layers, proximity to land surface, excess agricultural and industrial activities in south part and groundwater flow direction that is generally from north to south parts in this area makes south region of Shush plain especially vulnerable to heavy metals pollution and other contaminants.