During prolonged tetanization of a single medullated nerve fiber of Xenopus, the membrane potential at the end of an interspike interval may attain a value either slightly above or below that of the previous resting level. If interspike hyperpolarization occurs, both rise time and magnitude of the subsequent posttetanic hyperpolarization vary inversely with the extent to which the membrane potential has already been hyperpolarized at the end of the last interspike interval. If the passive transient posttetanic depolarization obtained after either lithium treatment or cyanide poisoning is algebraically substracted from the normal response, it is then possible to obtain a curve with a maximum voltage at a time very near that for termination of the stimulus volley. These findings, together with the observation that imposed conditioning hyperpolarizing currents are without significant effect on the normal posttetanic response, provide consistent evidence in favor of an electrogenic mechanism. Depletion of external potassium ions either leads to augmentation of the posttetanic hyperpolarization or produces no effect.