Vasoactive substances have long been suspected to be of importance in the genesis of migraine. In vitro experiments carried out by us and partially published, resulted in significant data concerning the contracting activity of migraineiurs' sere on various isolated organs. In the present study, extracranial animal arteries were tested by means of blood samples taken under identical conditions. No contracting activity from sere taken both in the headache-free period and during the migraine crisis was observed in animal arteries. By contrast, each serum taken after the onset of the migraine crisis, showed a synergic effect on the action of histamine, serotonin and bradykinin. This synergic effect increases with the worsening of the attack, while it decreases as soon as the attack wears off.The experiments on human specimens provided data which cannot be evaluated yet. It seems likely that, on the occasion of the migraine attack, vasoactive substances which enable isolated organs to contract In vitro are released or activated. They synergistically increase the activity of serotonin and histamine.