The pathophysiology of arterial vasospasm following subarachnoid hemorrhage (SAH) is poorly understood and the contribution of endogenous neuropeptides has not been sufficiently elucidated. Recently, we detected an excessive release of vasoconstrictive neuropeptide Y (NPY) in SAH patients and identified a significant correlation of NPY cerebrospinal fluid (CSF) levels with vasospasm-related ischemia. Here, we present the results of an experimental study on the possible role of the potent endogenous vasodilator calcitonin-gene related peptide (CGRP) in the acute stage of SAH. Twelve consecutive patients with SAH were included. Seven patients had severe arterial vasospasm, confirmed by transcranial doppler-sonography (TCD). Prospectively, CSF was collected from day 1 to day 10 after onset of the SAH. The levels of CGRP were determined in a competitive enzyme immunoassay and were correlated with the clinical course and hemodynamic changes. A cohort of 29 patients without CNS disease served as a control. CGRP was significantly higher in SAH patients compared with the control group (p<0.05). From day 1 to day 4, the CGRP levels in patients without vasospasm were significantly higher than the levels of CGRP in patients with vasospasm (p<0.05). These patients did not develop cerebral ischemia. The significantly increased levels of the CGRP during the first days after onset of the SAH in the non-vasospasm group indicate a potential protective role of CGRP. CGRP may alleviate arterial vasoconstriction and thus protect the brain from vasospasm and subsequent ischemia.