BACKGROUND: Deep brain stimulation (DBS) has re-emerged as an alternative therapy for intractable epilepsy. In this study, we investigated the feasibility, efficacy and safety of long-term anterior thalamic nucleus (ATN) stimulation for intractable epilepsy. METHODS: In this open-label pilot study of electrical stimulation of the ATN, we investigated four cases of intractable epilepsy (one man with generalized seizure, and three woman with partial seizure and secondary generalization; age range, 18-45 years), with a follow up of 2 years. Under the indication of bilateral or nonlocalized epileptic foci, each patient underwent stereotactic implantation of a quadripolar stimulating electrode in the bilateral ATN, guided by single-unit microelectrode recording. The stimulator was turned on after a sham period of 2-4 weeks. Seizure frequency was monitored and compared with the pre-implantation baseline. Twenty-one similar cases reported in the literature during the past 20 years were reviewed. RESULTS: Insertion into and stimulation through electrodes implanted in the ATN decreased seizure frequency, with a mean reduction rate of 49.6% in the current series. Two patients had seizure reductions of > or = 60%, with complete remission achieved in one patient. These findings were consistent with those in four other investigations of intractable epilepsy, which showed an overall rate of 45-55% in seizure reduction. One of our patients suffered a small frontal hemorrhage, and a second patient had extension erosion over the scalp; however, no resultant major or permanent neurological deficits were observed. CONCLUSIONS: Based on our study results and literature review, it appears reasonable to conclude that long-term ATN stimulation is a safe and effective treatment for seizure reduction in patients with intractable epilepsy.