BACKGROUND: Vagus nerve stimulation (VNS) has been shown to improve memory. OBJECTIVE: The purpose of this study was to learn at which stage of memory formation this influence occurs. METHODS: Ten subjects who had been implanted with vagus nerve stimulators for the treatment of intractable seizures performed tasks that assessed learning and retention (Hopkins Verbal Learning Test) during actual and sham VNS. RESULTS: We found that VNS had no effect on learning but enhanced consolidation, which led to improved retention. CONCLUSIONS: The means by which VNS improves retention is probably related to the increased activity in the nucleus of the tractus solitarius and the locus coeruleus-central adrenergic system that activates the amygdala and increases long-term potentiation in the hippocampus. Copyright © 2006 by Lippincott Williams & Wilkins.