We describe the identification of a novel drug, GR43175, for the acute treatment of migraine. GR43175 is a tryptamine analogue with a very selective agonist action at a 5-HT1-like receptor subtype first identified in the dog saphenous vein. Using this drug as a research probe, we have now shown that this 5-HT receptor type predominates in the carotid circulation, which explains the remarkably selective vasoconstrictor action of GR43175 in vivo in the carotid arterial bed of dogs and cats. Its vasoconstrictor action can be shown to be localized even further to arteriovenous anastomoses (shunts) within the carotid circulation, in such a way that blood flow to the brain as well as to extracerebral capillary beds remains unaffected or may even be increased. In the treatment of migraine demonstrated to date, the impressive effectiveness of GR43175 must reinforce the evidence in favour of an important vascular component being involved in the aetiology of the disease. The question is again raised as to whether the opening of carotid shunts is involved, as suggested by Heyck. If not, an alternative vascular locus needs to be identified.