The present study was to determine the impact of exposure to chronic stress on the levels of neurotrophic factors in the mouse brain, and investigate whether the stress induced decline in reproductive hormone may implicate this process. Intact adult male mice and gonadectomized ones were exposed to the scheduled stress episode for 60 consecutive days. The protein levels of brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT 3) were significantly decreased in the dentate gyrus, CA1, CA2 and CA3 subfields of the hippocampus and in the cerebral cortex, consistently, these brain regions showed significantly neurodegeneration in intact stressed mice. Interestingly, the stress induced diminution of BDNF and NT 3 protein levels in these brain regions were significantly intensified by gonadectomy. Particularly, NT 3 level in the dentate gyrus of stressed mice was preferentially decreased by gonadectomy. Likewise, the stress induced neurodegeneration in these brain regions, especially the dentate gyrus was also aggravated by gonadectomy. The results demonstrate that chronic stress decreases NT 3 and BDNF protein levels and produces neurodegeneration in the hippocampus and the cerebral cortex, and gonadectomy exacerbates these deleterious effects of chronic stress on the brain, indicating that gonadectomy increases the vulnerability of neurons to neuropathology of stress, and suggesting that stress induced testosterone deficit play a contributive role in neurodegeneration. This study also suggests that the diminishments of BDNF and NT 3 protein levels contribute to the neurodegeneration in the brain during chronic stress.