The presumed linear relationship describing the contribution of nitrous oxide (N2O) to the enflurane requirement necessary to achieve a 1.0 MAC level of anesthesia was tested in rats (N = 84). Each rat received one of six different concentrations of N2O, and enflurane was adjusted to attain 1.0 MAC with the use of a standard tail clamp method. The resultant group MAC anesthetic concentrations were Group I-N2O = 0.0%, enflurane = 2.30%; Group II-N2O = 10.4%, enflurane = 2.19%; Group III-N2O = 30.7%, enflurane = 1.85%; Group IV-N2O = 61.8%, enflurane = 1.75%; Group V-N2O = 70.9%, enflurane = 1.56%; and Group VI-N2O = 80.3%, enflurane = 1.54%. Increasing the N2O concentration from 0-10%, from 30-60%, or 70-80% did not significantly decrease the enflurane requirement; however, increasing the N2O concentration from 10-30% or 60-70% produced a significant decrease (P less than 0.05) in the concentration of enflurane required for 1.0 MAC of anesthesia. Thus, in rats, increasing the concentration of N2O in sub-MAC ranges did not produce a linear decrease in the enflurane concentration required to add up to 1.0 MAC of anesthesia. These results are consistent with a dose-dependent interaction between N2O and the excitatory properties of enflurane; this interaction could represent synergism at low concentrations or antagonism at higher concentration of N2O.