Background The authors hypothesized that perioperative lymphocytopenia is partially caused by apoptosis of lymphocytes Induced by Inhalation anesthetics. Therefore, they evaluated whether sevoflurane and isoflurane induce apoptosis of normal peripheral lymphocytes. Methods: Normal peripheral blood mononuclear cells were exposed to sevoflurane and isoflurane, and the percentages of apoptotic lymphocytes was measured by Annexin V-fluorescein isothiocyanate-7-amino actinomycin D flow cytometry after 24 h of exposure (0.5, 1.0, and 1.5 mM) and after 6, 12, and 24 h of exposure (1-5 mm). The percentages of lymphocytes with caspase 3-like activity were also measured after 24 li of exposure (1.5 mM). Results: The percentages of apoptotic lymhocytes were increased in a dose-dependent manner (controls: 5.1 +/- 1.4%; sevoflurane: 7.3 +/- 1.3% [0.5 mM], 9.1 +/- 1.5% [1.0 mM], 12.6 +/- 2.1% [1.5 mM]; isoflurane: 7.5 +/- 1.6% [0.5 mM], 10.5 +/- 1.5% [1.0 mM], 16.3 +/- 2.70% [1-5 mM]) after 24 h of exposure and in a time-dependent manner (controls: 1.2 +/- 0.4% [6 h], 3.4 +/- 0.7% [12 h], 5.6 +/- 1.2% [24 h]; sevoflurane: 1.8 +/- 0.4% [6 h], 6.4 +/- 1.2% [12 h], 11.3 +/- 2.2% [24 h]; isoflurane: 2.6 +/- 0.5% [6 h], 8.8 +/- 1.5% [12 h],16.0 +/- 1.9% [24 h]) at the concentration of 1.5 mM. The percentages of lymphocytes with caspase 3-like activity were increased (controls: 10.0 +/- 1.1%; sevoflurane: 13.8 +/- 1.2%; isoflurane: 17.0 +/- 1.3%). Conclusions. Both sevofluraine and isoflurane Induced apoptosis; in peripheral lymphocytes in dose-dependent and timedependent manners in vitro.