Neuropeptide Y (NPY) is widely distributed throughout sympathetic nerve endings where it is co-stored and co-secreted with noradrenaline. It is considered a marker of noradrenergic function. To determine the role of NPY in the pathogenesis of juvenile headache, we determined its plasma levels in two groups of young migraine patients (with and without aura), in a group of episodic tension-type headache patients and in a group of age and sex-matched healthy subjects. Significantly lower plasma levels of NPY were evident in the migraine patients with aura (P<0.001) and, to lesser extent, in the migraine patients without aura (P<0.02), both assessed in the interictal period, with respect to the control group. Plasma NPY levels tended to significantly increase during attacks in migraine patients with aura (P<0.0009). A less evident, though significant increase was also present during attacks in migraine patients without aura (P<0.02). No significant variations were observed between headache-free periods and attacks in tension-type headache patients. Reduced NPY levels in the interictal period can be considered further evidence of the derangement of the sympathetic function in the course of migraine, particularly that with aura. The increase in NPY levels during migraine attacks could be an expression of sympathetic activation, even though the functional status of this system is less efficient.