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Hypothermia often occurs during surgery, a factor influencing anesthetic pharmacokinetics through its influence on solubility. Information on the tissue solubility of volatile anesthetics under hypothermia is limited. The present study supplies this information for the solubility of volatile anesthetics in human tissues. Tissue specimens of brain, heart, liver, muscle, and fat were obtained from 10 postmortem males (27 ± 8 yr). Tissue/gas partition coefficients of desflurane, sevoflurane, enflurane, isoflurane and halothane were measured at 37°C, 33°C, 29°C, 25°C, 21°C, and 17°C. For each given tissue, the order of tissue/gas partition coefficient was halothane >enflurane >isoflurane >sevoflurane >desflurane. Tissue/gas partition coefficients at 37°C differed significantly (P < 0.05) across drugs, except that liver/gas partition coefficients for isoflurane and enflurane did not differ. The logarithm of all tissue/gas partition coefficients increased linearly with decreasing temperature (P < 0.05). In conclusion, hypothermia increases tissue/gas partition coefficients of volatile anesthetics. The increases are proportional to those for blood/gas partition coefficients, and therefore tissue/blood partition coefficients will not change during hypothermic conditions.