A selective breeding process designed to produce mice resistant (HI mice) and susceptible (LO mice) to nitrous oxide anesthesia was continued through 10 generation. At the tenth generation, the nitrous oxide requirements of the HI and LO mice (as measured by the partial pressure of nitrous oxide required to abolish the righting reflex) were separated by more than 0.7 atm. The HI mice also had a higher anesthetic requirement for cyclopropane, enflurane, isofluranc, halothane, and methoxyflurane, as measured by response to a tail-clamp stimulus. HI mice given an intraperitoneal injection of ethanol (4 g/kg) had 44 per cent shorter sleep times and 12 per cent higher blood alcohol levels upon awakening than did LO mice. For nitrogen, argon, cyclopropane, isoflurane, enflurane, halothane, and methoxyflurane, we determined the doses at which the righting reflex was abolished in HI and LO mice. The separation in righting-reflex ED50s between these two lines was inversely related to the lipid solubility of the anesthetic. For the most lipid-soluble anesthetic, methoxyflurane, no significant differences in potency, as measured by the righting-reflex ED50, could be detected between the HI and LO mice. In contrast, the separation in anesthetic requirements, as measured by the tail-clamp ED50, was approximately the same for each of the anesthetics tested.