This research examined the electrophysiological, behavioral and neuroanatomical changes following an injection of kainic acid (KA) which destroyed most of the CA3 pyramidal cells in the hippocampus. For 5 days following the injection of KA, the evoked potential (EP) in the CA1 pyramidal cells produced by stimulation of the perforant path (PP), dentate gyrus (DG), or remaining CA3 cells was markedly altered. These rats also had an impairment of choice accuracy in a discrimination task that required working memory. Within 30 days, however, all EPs had become more normal. Choice accuracy had either returned to criterion levels, or improved substantially above that immediately following the KA injection. Analysis of the EPs indicated that the normal trisynaptic pathway through the hippocampus had been re-established. Neuroanatomical examination of the remaining CA3 pyramidal cells showed a marked increase in cross-sectional area. These data provide an electrophysiological description of the effects of KA on neuronal transmission in the hippocampus, and suggest that the behavioral recovery following these injections was due to sprouting of the remaining CA3 cells which re-established the trisynaptic pathway in the hippocampus.