To determine the percentage of anesthetic metabolized and to assess the role of metabolism in the total elimination of inhaled anesthetics, the authors administered isoflurane, enflurane, halothane, and methoxyflurane simultaneously, for 2 h, to nine healthy patients. Total anesthetic uptake during the 2 h of washin and total recovery of unchanged anesthetic in exhaled gases during 5 to 9 days of washout were measured, and from these the per cent of anesthetic uptake that was recovered was calculated. Of the isoflurane taken up, 93 +/- 4% (mean +/- SE) was recovered. To compensate for factors other than metabolism that limit complete recovery of unchanged anesthetic, the percentage recovery of each anesthetic was normalized to the percentage recovery of isoflurane (which it was assumed undergoes no metabolism). Deficits in normalized recovery were assumed to be due to metabolism of the anesthetics. The resulting estimates of metabolism of anesthetic taken up were: enflurane 8.5 +/- 1.0%, halothane 46.1 +/- 0.9%, and methoxyflurane 75.3 +/- 1.6%. These results indicate that elimination is primarily via the lungs for isoflurane and enflurane, equally via the lungs and via metabolism for halothane, and primarily via metabolism for methoxyflurane.