OBJECTIVE: We recently found that Hering's nerve stimulation (HNS) effectively blunts seizure activity. This study characterizes the cortical areas that are activated by HNS. METHODS: Hering's nerve (HN) was stimulated in 3 dogs and 6 pigs, and then the brains of the animals were removed. The insular and mesial temporal cortices were removed and evaluated for increased neuronal activity by examining Fos-like activity. RESULTS: In both the dogs and pigs, Fos activity was elevated in the anterior insular and mesial temporal cortices. Increased cortical activity was not noted in adjacent areas such as the frontal cortex. CONCLUSION: This study demonstrates that the mesial temporal and anterior insular cortices are selectively activated by stimulation of HN, thus suggesting cortical loci at which HNS might blunt seizure activity.