Objectives. Val66Met BDNF gene polymorphism is shown to affect the function of mature BDNF and mature BDNF plays an important role in the hippocampal neurogenesis and neuronal survival. Methods. A relationship of Val66Met BDNF gene polymorphism and hippocampal volumes in 33 MDD patients and 40 healthy controls is investigated. Region of interest analysis was conducted on the images acquired via MRI. Results. Depressed patients had smaller left hippocampal volumes compared to healthy controls. The diagnosis of MDD was not significantly related to hippocampal volumes among Met carriers; however, among Val homozygotes depressed patients had significantly smaller left hippocampal volumes compared to controls. Although both right and left hippocampal volumes showed nearly significant correlation with the duration of illness, this correlation reached (negative) significant levels only in the right hippocampal volume of the Val homozygotes. Conclusions. Val homozygote genotype may serve as a vulnerability factor in MDD regarding hippocampal volume loss. This finding can be considered as a supportive evidence for the neurotrophic factor hypothesis of depression.