Tumor necrosis factor (TNF)-beta has been implicated in the regulation of immune system. Alterations of the immune system in patients with major depressive disorder (MDD) have been also proposed to date. The present study was undertaken to investigate whether TNF-beta gene polymorphism is associated with MDD in the Korean population. Ninety-five patients with MDD who met the criteria of DSM-IV and 202 gender- and age-matched unrelated volunteers participated in the study. Genotyping for TNF-beta gene was performed by a polymerase chain reaction-restriction fragment length polymorphism method. The genotype and allele distribution in patients with MDD was similar to that of the controls. This study suggests that the TNF-beta gene polymorphism does not confer a susceptibility to MDD in the Korean population. A larger scaled study to examine different races is necessary to determine a role in the pathogenesis of MDD.