Glutathione- S -Transferase (GST) might be involved in the initial reduction of arsenate to arsenite and subsequent oxidative methylation (Sampayo 2000, Zakharyan 2001). Humans with null genotype of GST M1 and T1 have been considered to be a high risk group of people who retain arsenic in their body due to incomplete metabolism of arsenic.In order to elucidate the relationship among clinical severity, urinary excretion of arsenic and genetic polymorphisms of GST M1 and T1, a total of 100 study subjects were recruited from the villages of southern region of WestBengal, India. Specimens of drinking water, blood and urine were collected from each study subjects. Concentration of arsenic in urine and water was determined by atomic absorption spectro photometry-hydride generation system. Multiplex polymerase chain reaction (PCR) was performed to determine the genetic polymorphism of GST M1 and T1. Genetic polymorphism of GSTM1 and T1 were significantly associated (p<0.05) with Clinical severity in higher exposure groups. Persons having null genotype have an increased clinical symptom score than persons with GSTM1 or GST T1 nonnull genotype. Persons with GSTM1 or GST T1 null genotype have decreased total urinary arsenic compare to persons having non null genotype.