Introduction: The serotonin transporter (5-HTT) gene is known as the responsible gene for interindividual variation and the genetic susceptibility for psychiatric diseases, such as bipolar mood, schizopherenia and major depression. The protein which is encoded by 5-HTT gene is involved in the reuptake of serotonin in to the presynaptic space. A common polymorphism in its upstream regulatory region, modulate the efficiency of 5-HTT transcription. This polymorphism (5-HTTLPR) is caused by difference in the number of GC rich, repetitive elements. Deletion or insertion in the 5-HTTLPR creates a short allele (14 repeats), and a long allele (16 repeats). Transcription of the L allele is 20 times more than the S allele. Since the serotonin and its transporter are involved in mood control, they can be targeted by antidepressant medications, and specially the selective serotonin reuptake inhibitor: Citalopram Materials and Methods: First of all, in order to estimate the frequency of each allele in the Iranian normal population,we genotyped 100 control samples. then the response of 100 patients suffering from major depression disorder, to Citalopram, and its association with their genotypes were investigated. Our method includes PCR followed by running on agarose gel. And DHPLC to determine the concentration of the drug in the blood plasma of patients. Results frequency of the L allele Among patients with response to Citalopram was 77%, and that of the S allele was 23%. whereas 70% of patients who didn't response to Citalopram had the S allele, and just 30% of them were caring the L allele. Conclusion: Our results confirmed the result of the same studies in this field in Japanese , Chines, and Spanish population. and is appose to the result of Korean population.