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Aim: To investigate the stress-induced apoptosis of natural killer (NK) cells and the changes in their killing activity in mouse livers., Methods: A restraint stress model was established in mice. Flow cytometry was employed to measure the percentage of NK cells and the changes in their absolute number in mouse liver. The cytotoxicity of hepatic and splenic NK cells was assessed against YAC-1 target cells via a 4 h 51Cr-release assay., Results: The restraint stress stimulation induced the apoptosis of NK cells in the liver and the spleen, which decreased the cell number. The number and percentage of NK cells in the spleen decreased. However, the number of NK cells in the liver decreased, whereas the percentage of NK cells was significantly increased. The apoptosis of NK cells increased gradually with prolonged stress time, and the macrophage-1 (Mac-1)(+) NK cells were more susceptible to apoptosis than Mac-1(-) NK cells. Large numbers of Mac-1(-) NK cells in the liver, which are more resistant to stress-induced apoptosis, were observed than the Mac-1(-) NK cells in the spleen. The stress stimulation diminished the killing activity of NK cells in the spleen was significantly decreased, but the retention of numerous Mac-1(-) NK cells in the liver maintained the killing ability., Conclusion: Significant stress-induced apoptosis was observed among Mac-1(+) NK cells, but not Mac-1(-) NK cells in the mouse liver. Stress stimulation markedly decreased the killing activity of NK cells in the spleen but remained unchanged in the liver.