The pathogenesis of ruptured intracranial aneurysms and cervical artery dissections is poorly understood but may be similar in these two disorders. We report four patients with alpha 1-antitrypsin deficiency who developed a ruptured intracranial aneurysm or spontaneous dissection of the cervical internal carotid artery. Three patients were heterozygous for the deficient allele (PiMZ or PiGZ) and one was homozygous (PiZZ). A deficiency of alpha 1-antitrypsin or one of the other protease inhibitors could result in degradation of the arterial wall through an imbalance between proteolytic enzymes and their inhibitors, thereby predisposing the arterial wall to dissection or aneurysm formation.