Norepinephrinergic neurotransmission in the central nervous system appears to have a major impact on the symptomatology in major depressive disorder and the human norepinephrine transporter (NET) gene is one of the key candidates for genetic studies in major depressive disorder. The authors established a new allele-specific PCR-based genotyping procedure and examined whether the NET T-182C polymorphism was associated with the susceptibility to major depressive disorder in a Japanese population. This study included 145 patients with major depressive disorder (according to DSM-IV) and 164 healthy volunteers. There was a significant difference in the genotype distribution between major depressive disorder patients and healthy volunteers (p = 0.02), and the C/C genotype was associated with lesser susceptibility to major depressive disorder. The NET T-182C polymorphism may be in part related to the pathophysiology of major depressive disorder in a Japanese population.