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The low solubility of sevoflurane in blood suggests that this agent should enter and leave the body more rapidly than isoflurane. However, the closeness of sevoflurane and isoflurane tissue/blood partition coefficients suggests that the rates of equilibration with and elimination from tissues should be similar. We tested both predictions, comparing sevoflurane with isoflurane and nitrous oxide in seven volunteers. We measured the rate at which the alveolar (end-tidal) (FA) concentration of nitrous oxide increased toward an inspired (FI) concentration of 65%–70%, then measured the concurrent rise in FA and mixed expired concentrations (FM) of sevoflurane and isoflurane at respective FI values of 1.0% sevoflurane and 0.6% isoflurane for 30 min. Minute ventilation (V E) was measured concurrently with the measurements of anesthetic concentrations. For the potent agents, we also measured V E, FA and FM for 6–7 days of elimination. FA/FI values at 30 min of administration were as follows: nitrous oxide, 0.986 ± 0.003 (mean ± SD); sevoflurane, 0.850 ± 0.018; and isoflurane, 0.733 ± 0.027. FA/FA0 (FA0 = the last FA during administration) values after 5 min of elimination were as follows: sevoflurane, 0.157 ± 0.020; isoflurane, 0.223 ± 0.024. Recovery (volume of anesthetic recovered during elimination/volume taken up) of sevoflurane (101% ± 7%) equaled recovery of isoflurane (101% ± 6%). Time constants for a five-compartment mammillary model for sevoflurane were smaller than those for isoflurane for the lungs but were not different from isoflurane for the other compartments. In summary, we found (a) that FA/FI of sevoflurane increases and FA/FA0 decreases more rapidly than do these variables with isoflurane in humans; but (b) that elimination from tissues did not differ between sevoflurane and isoflurane; and (c) that the metabolism of sevoflurane did not differ from that estimated for isoflurane.