Although theoretical models predict uptake of inhaled anesthetics during closed-circuit anesthesia (CCA), clinical data for most anesthetics are conflicting or non-existent. In addition, the effects of patient characteristics and mode of ventilation on anesthetic uptake are unclear. Forty-one ASA physical status I or II adult patients undergoing a variety of 1-1.5 h surgical procedures were randomly allocated to receive CCA with desflurane or isoflurane with ventilation being either spontaneous or controlled. An end-expired anesthetic concentration of 1.3 minimum alveolar anesthetic concentration (MAC) was maintained by continuous injection of the liquid anesthetic into the circuit using a syringe pump. After an initial 4-min wash-in period, uptake during the first hour of CCA was nearly constant. Uptake was the same whether ventilation was spontaneous or controlled. Patient characteristics (age, height, weight, weight3/4, and body surface area) were comparable between groups and did not correlate with uptake. The virtually constant uptake after wash-in of desflurane and isoflurane contrasts with the square root of time model of Lowe and Ernst. These findings may greatly simplify CCA.