Introduction:Cluster headache is a particularly severe, periodic cephalalgia which is occasionally refractory to medical treatment. In the past, surgical lesions of the trigeminal nerve (TN) have produced initial relief in more than one-half of patients. Radiosurgical lesions of the TN have produced short-lived pain relief and perhaps increased toxicity. In this pilot study we added the sphenopalatine ganglion (SPG) as an additional target in an effort to extend the degree and length of pain relief. Methods: Over an 8-year period, we carried out 12 gamma knife radiosurgical treatments in 7 patients, treating only the TN or later both the TN and SPG contemporaneously. A 4-mm collimated shot was placed on the nerve root entry zone of the TN and a maximum dose of 85 to 103 Gy was prescribed. The SPG was radiated in the pterygopalatine fossa using an 8-mm collimated shot and maximum dose of 85 to 97 Gy. Results: One patient with three treatments to the TN enjoyed immediate and complete relief for 5, 22, and 25 months. Four of 5 patients with radiation of both the TN and SPG experienced pain relief for 8 and 30 months, or are continuing to enjoy pain relief 7, 18, and 22 months after treatment or re-treatment at the last follow-up. Most patients reported facial paresthesias following radiation. No profound numbness or deafferentation pain was experienced. Conclusions: These results, in some respects, refl ect the morbidity and pain relief experience of Gamma Knife ® radiosurgery for classical trigeminal neuralgia. The addition of the SPG as a target may prove to be valuable and has not increased the morbidity of treatment.