ObjectiveDetermine the effects of serial episodes of anoxia in an in vitro peripheral nerve preparation. MethodsThe nerve action potential (NAP) from rat sciatic nerve was recorded during 5 cycles of anoxia and reperfusion. Multiple NAP parameters were analyzed as well as stimulus response curves. ResultsThe amplitude of the NAP declined to half baseline in 865s on the first cycle of anoxia and recovered to half baseline during recovery in 470s. These times increased with successive cycles of anoxia. The current required to produce a half maximal NAP showed a variable initial decrease before increasing with anoxia. The paired-pulse response showed a decline at 2–3ms interstimulus interval during anoxia but was less dependent of interstimulus interval during recovery. NAP amplitude and velocity decrease over successive cycles of anoxia at a rate greater than in the absence of anoxia. ConclusionsThe NAP declines slowly when peripheral nerve is exposed to anoxia but returns at least twice as quickly when re-exposed to oxygen. Short periods of anoxia produce long lasting changes in the nerve suggesting greater resistance to anoxia. With serial episodes of anoxia there is gradual NAP amplitude reduction and increase in duration and latency. SignificanceAnoxic-preconditioning appears in isolated peripheral nerve.