Brain-derived neurotrophic factor (BDNF), which regulates neuronal survival, growth, differentiation and synapse formation, broadly regulates the stress response.1 A common single-nucleotide polymorphism in the BDNF gene (Val66Met) influences hippocampal volume,2 memory3 and appears related to susceptibility to a variety of neuropsychiatric disorders, including posttraumatic stress disorder (PTSD).1 Therefore, we hypothesized that BDNF may be an important mediator of the abnormal stress response contributing to PTSD. We analyzed genetic variation in 461 and the plasma levels of BDNF in 68 US. Army Special Operations soldiers deployed during the Iraq and Afghanistan wars. A probable-PTSD diagnosis was made if subjects endorsed Diagnostic and Statistical Manual of Mental Disorders-IV PTSD criteria (at least one re-experiencing, three avoidance and two hyper-arousal symptoms) and had a total PTSD check list (PCL) score of 50 or above (see Supplementary Methods). We found that 42 (9%) participants met criteria for probable-PTSD, while the remaining 419 (91%) subjects did not. In those with probable-PTSD, the frequency of Met/Met was nearly threefold higher than in the controls. The allelic frequency of Met was twofold higher in individuals with probable-PTSD than in controls (Supplementary Information). BDNF levels in plasma of the subjects with PTSD were significantly higher than those in the non-PTSD controls. These results agree with evidence suggesting that BDNF is involved in the development of PTSD.1 Met carriers have a smaller hippocampus volume, relative to controls2 and perform more poorly than controls (Val/Val) on memory tasks.4 Veterans with psychotic PTSD carry more Met alleles than non-psychotic veterans with PTSD or veterans without PTSD,5 even though a case–control genetic association study showed no relationship between BDNF gene Val66Met and PTSD diagnosis.6