Objective To determine the combined effect of hypothermia and crystalloid hemodilution on blood solubility of volatile anesthetics.Methods Two hundred and thirty ml blood samples obtained from each of twelve healthy male volunteers were adjusted to a hematocrit of 40% and then diluted with normal saline to hematocrits of 36%, 32%, 28%, 24%, and 20%. Blood/gas partition coefficients of desflurane, sevoflurane, isoflurane, enflurane and halothane were measured at 37℃, 33℃, 29℃, 25℃, 21℃ and 17℃ using a two-stage headspace double equilibration method.Results As the temperature decreased, the logarithm of the blood/gas partition coefficient increased linearly (P<0.05). As the hematocrit decreased, the logarithm of the blood/gas partition coefficient decreased linearly (P<0.05). The combined effect of hypothermia and crystalloid hemodilution on blood solubility of anesthetics was expressed by multiple linear regression equations as follows:Desflurane: logeλB/G=-0.0302×T+0.0094×HCT+0.119 R2=0.973Sevoflurane: logeλB/G=-0.0295×T+0.0092×HCT+0.306 R2=0.961Isoflurane: logeλB/G=-0.0382×T+0.0154×HCT+1.120 R2=0.997Enflurane: logeλB/G=-0.0408×T+0.0198×HCT+1.408 R2=0.982Halothane: logeλB/G=-0.0417×T+0.0218×HCT+1.649 R2=0.994Where λB/G is the blood/gas partition coefficient, T is temperature (℃) and HCT is hematocrit (%).Conclusions Hypothermia increases, while crystalloid hemodilution decreases the blood solubility of volatile anesthetics. The combined effect of hypothermia and hemodilution on blood solubility at any cross point of temperature from 37℃ to 17℃ and hematocrit from 40% to 20% could be predicted by the multiple linear regression equations developed in this study.