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A computer program that models anesthetic uptake and distribution has been in use in our department for 20 yr as a teaching tool. New anesthesia machines that electronically measure fresh gas flow rates and vaporizer settings allowed us to assess the performance of this model during clinical anesthesia. Gas flow, vaporizer settings, and end-tidal concentrations were collected from the anesthesia machine (Datex S/5 ADU) at 10-s intervals during 30 elective anesthetics. These were entered into the uptake model. Expired anesthetic vapor concentrations were calculated and compared with actual values as measured by the patient monitor (Datex AS/3). Sevoflurane was used in 16 patients and isoflurane in 14 patients. For all patients, the median performance error was −0.24%, the median absolute performance error was 13.7%, divergence was 2.3%/h, and wobble was 3.1%. There was no significant difference between sevoflurane and isoflurane. This model predicted expired concentrations well in these patients. These results are similar to those seen when comparing calculated and actual propofol concentrations in propofol infusion systems and meet published guidelines for the accuracy of models used in target-controlled anesthesia systems. This model may be useful for predicting responses to changes in fresh gas and vapor settings.