When reducing fresh gas flows, the course of the vaporizer dial settings required to maintain a constant end-expired concentration of a potent inhaled anesthetic becomes more dependent on the uptake pattern of the inhaled anesthetic. However, the uptake pattern of potent inhaled anesthetics during prolonged procedures remains poorly quantified. Therefore, we determined isoflurane and desflurane uptake (V(iso) and V(des), respectively) during liver resection (LR, n = 17) and orthotopic liver transplantation (OLT, n = 18) using a liquid injection closed-circuit anesthesia technique maintaining the end-expired concentration at 0.8% and 4.5%, respectively. Individual and average uptake curves were fit to a series of mathematical functions and compared with the square root of time and four-compartment models. Cumulative doses of isoflurane and desflurane after 1 and 3 h in the LR group and after 1, 3, and 8 h in the OLT group were correlated with demographic variables and each patient's average cardiac output and cardiac index. Average uptake was best described by a biexponential fit: V(iso) (LR) = 1.5 x (1 - e(-t x 0.525)) + 16.4 x (1 - e(-t x 0.00506)) (R(2) = 0.9996); V(iso) (OLT) = 1.4 + 3.1 x (1 - e(-t x 0.472)) + 26.7 x (1 - e(-t x 0.00307)) (R(2) = 0.9994); V(des) (LR) = 2.7 x (1 - e(-t x 0.763)) + 28.7 x (1 - e(-t x 0.00568)) (R(2) = 0.9984); and V(des) (OLT) = 1.4 x (1 - e(-t x 0.472)) + 26.7 x (1 - e(-t x 0.00307)) (R(2) = 0.9994). Uptake showed significant interindividual variability, and correlations between uptake variables and patient characteristics were inconsistent. The rate of uptake decreased more slowly then predicted by the uptake models. Because neither existing models nor patient characteristics accurately predict uptake in the individual patient, anesthesia techniques involving the use of low fresh gas flows will continue to have to rely on drug monitoring. However, the slowly decreasing rate of uptake during prolonged procedures suggests that the number of vaporizer adjustments to keep the end-expired concentration constant should be limited.