Consistent evidence demonstrates that migraine is far more common in women than in men, but the explanations for this preponderance have not been systematically evaluated. We examined whether the female preponderance is attributable to genetic factors using data from a controlled family study which included 260 probands and their 1232 first-degree adult relatives. We found that although the risk of migraine was three times greater among the relatives of probands with migraine compared with controls, there was no differential risk of migraine among the relatives of male vs. female probands with migraine. Taking these data together with other family studies, we conclude that the increased risk of migraine in females is likely to result from increased exposure to non-familial endogenous or exogenous risk factors for migraine that lower the threshold for expression of migraine in women.