Mice manifest a characteristic withdrawal syndrome after 1 h of exposure to N2O due to a rapidly developing tolerance to N2O. The inspired concentrations that cause loss of the righting reflex in mice (i.e., the ED50) in the presence of 1 atm of O2 of: N2O alone, cyclopropane alone, N2O plus 13.6 atm He and ethylene plus 13.6 atm He were determined. In each instance the ED50 was determined after averages of 6, 34 and 64 min of exposure to the anesthetic agents. For N2O alone the ED50 at 6 min was 1.18 .+-. 0.049 atm increasing to 1.39 .+-. 0.061 atm at 64 min. For ethylene plus He the ED50 increased from 1.21 .+-. 0.033 atm at 6 min to 1.31 .+-. 0.039 atm at 64 min, indicating the development of acute tolerance. Neither cyclopropane alone nor N2O plus He caused acute tolerance. This absence of tolerance may be due to a slower development of an alveolar anesthetic concentration.