Anesthetic requirements for nitrous oxide, cyclopropane, enflurane, and isoflurane were determined in quaking mice (autosomal recessive mutants with a deficiency in central nervous system myelin) and their littermate (non-quaking) controls. Although quaking mice had significantly (15 to 23 per cent) lower nitrous oxide and cyclopropane rolling-response ED50S than did littermate controls, enflurane and isoflurane rolling-response ED50S were not significantly different. Tail-clamp ED50S for cyclopropane, enflurane, and isoflurane in quaking and control mice were not significantly different. Myelin from quaking mice showed higher levels of palmitic, stearic, and docosahexaenoic acids, lower levels of oleic, eicosenoic, and docosatetraenoic (and/or nervonic) acids, and a lower cholesterol/phospholipid ratio. In contrast, the phospholipid, fatty acid, and cholesterol compositions of synaptic plasma membranes isolated from quaking and control mice were essentially identical. It is concluded that gross alterations in the lipid composition of central nervous system myelin have little or no influence on anesthetic requirement.