Many authors have reported an association between the angiotensin-converting enzyme (ACE)-D allele and coronary heart disease and other cardiovascular diseases. The mechanism underlying the positive associations between the ACE-D alleles and diseases are not yet clear. Alterations of the renin-angiotensin system have been implicated in the pathogenesis of various diseases. Recently, several angiotensin I-converting enzyme (ACE) inhibitors and an angiotensin II receptor blocker were demonstrated to have a clinically important prophylactic effect in migraine. ACE is one of the key enzymes in the rennin-angiotensin-aldosterone system, which modulates vascular tension and blood pressure. Previous reports showed an association between migraine without aura. ACE-D allele polymorphism. The study is aimed to evaluate if the DD genotype could also be associated with the frequency and duration of migraine without aura and with migraine with aura (MwA). We analyzed the ACE insertion (I)/deletion (D) genotypes of 54 patients suffering from migraine with aura (MwA), 46 from migraine without aura and 100 healthy controls. The ACE D allele were significantly more frequent in the MwA than controls. Patients with migraine without aura showed higher incidence of the ACE-DD gene than control subjects There seems to be a possible relationship between ACE activity and the pathogenesis of migraine. Our data suggest that ACE-DD gene polymorphism could have an important role in determining migraine attacks and the frequency of these attacks. Further data are needed through further studies, especially on the biomolecular level.