Objective: To determine whether calcitonin gene-related peptide participates in the attacks of trigeminal neuralgia and to get a deeper understanding about its pathogenic mechanism. Methods: Seven patients were studied. During the attacks, venous blood was sampled from both the external jugular vein and the cubital fossa vein ipsilateral to the pain; after operations the venous blood from the external jugular vein was sampled again. Plasma levels of calcitonin gene-related peptide were determined using sensitive radioimmunoassays. Results: During the attacks of trigeminal neuralgia, the levels of calcitonin gene-related peptide in the external jugular vein blood were significantly higher than that in cubital fossa vein blood and postoperative external jugular vein blood. Conclusion: Excessive synthesis and release of calcitonin gene-related peptide in the trigeminal nerve may promote the release of substance P, cause the intense paroxysmal pain, and form a local neurogenic inflammation.