Patients with bitemporal epilepsy are characterized by the existence of independent bitemporal seizure onset zones. The aim of this study was to evaluate the effect of chronic vagal nerve stimulation (VNS) on eight patients with bitemporal epilepsy. We demonstrated the gradually increased effect of VNS on the reduction of seizures as compared with baseline seizure frequency in patients with bitemporal epilepsy. The average seizure reduction increased from 4.2% at the 3-month follow-up visit to 18.2, 34.4 and 42.2% at the 6, 12 and 18-month follow-up visits. Similarly, a >or=50% reduction of complex partial seizures was reported at the 3-month follow-up visit in no patients (0%); at the 6-month follow-up visit in one patient (12.5%); at the 12-month follow-up visit in three patients (37.5%); and at the 18-month follow-up visit in five patients (62.5%). These data demonstrate the positive and long-lasting effect of VNS on seizure reduction in patients with intractable bitemporal epilepsy. The main mechanism of this chronic effect is not fully understood.