Study Objective: There are few comparative studies of stress hormone changes during general anesthesia with long duration between isoflurane-nitrous oxide and sevoflurane nitrous oxide anesthesia. We investigated perioperative changes of stress hormone in these two anesthetic methods with duration of more than 10 hours. Design: Prospective study. Setting: Operating room and high care unit of a University hospital. Patients: Twenty patients with ASA physical status I or II for surgery for laryngeal or pharyngeal cancer with expected duration of more than 10 hours. Interventions: Anesthesia was induced with midazolam, thiopental, and vecuronium and was maintained with sevoflurane (sevoflurane group) or isoflurane (isoflurane group) with nitrous oxide 4 L/min in oxygen 2 L/min. Measurements and Main Results: Plasma concentrations of epinephrine, norepinephrine, cortisol, adrenocorticotropic hormone, and anti-diuretic hormone (ADII) serum concentrations of glucagon and insulin; and blood glucose concentration were measured before inhalation of anestheties, after 5 and 10 hours, and at 1, 6, and 12 hours after the end of inhalation. Epinephrine and norepinephrine concentrations increased continuously during and after surgery in the isoflurane group whereas it increased only after surgery in the sevoflurane group. Both concentrations were higher in the isoflurane group during anesthesia. Cortisol increased continuously whereas adrenocorticotropic hormone increased only during surgery. Anti-diuretic hormone increased with its peak during Surgery and the isoflurane group had significantly higher values than the sevoflurane group. Glucose increased both during and after surgery, insulin increased only after surgery, and glucagon decreased during surgery in both groups, Conclusions: In inhalation anesthesia with the duration of more than 10 hours, isoflurane, nitrous oxide and sevoflurane-nitrous oxide had the same effects on stress hormone changes except for epinephrine, norepinephrine, and ADH. Epinephrine, norepinephrine, and ADH concentrations were higher in isoflurane-nitrous oxide anesthesia. (c) 2005 Elsevier Inc. All rights reserved.