Different stressors, affecting the cells of target organs, can lead to genomic instability and even disintegration, which can play a role in the formation of post-stress pathologies. We studied the effect of psycho-emotional stressors (immobilization and mouse stress pheromone – 2,5-dimethylpyrazine) on the DNA integrity of hippocampal and bone marrow cell in male mice of CD1, CBA and C3H strains. Cytogenetic and immunocytochemical methods (alkaline comet assay, ana-telophase analysis of mitotic disturbances and analysis of γH2AX foci) were used. It is shown that the classic mouse stressor (immobilization or restraint), similar as 2,5-dimethylpyrazine, damages the genome of the cells of both organs studied. The destabilization of the cell genome of various organs is considered as an essential stage in the development of a stress response, which is an attempt of the organism to adapt to extreme environmental influences.