Migraine has been associated with diseases considered to be related to extracellular matrix disorders--in particular, cervical artery dissection. In this population-based study, we found a highly significant association between migraine and the activity of serum elastase, a metalloendopeptidase degrading specific elastin-type amino acid sequences. Such enzymes are involved in matrix degradation. This association was seen in both sexes and was stronger for migraine with aura. These findings could help in the understanding of why patients with migraine are at higher risk of stroke. Further study is needed to establish whether extracellular matrix abnormalities play a broader role in the pathophysiology of migraine.