Platelet 5-hydroxytryptamine (5-HT) is diminished during migraine headache and the injection of reserpine, which releases 5-HT from body stores, induces a typical headache in migrainous subjects. The intravenous injection of 5-HT relieves established migraine headache, but causes side-effects of nausea, faintness, paraesthesia and dyspnoea. The 5-HT1-like agonist sumatriptan exerts the beneficial effects of 5-HT with minimal side-effects. Receptors for 5-HT are present in cranial arteries and are also widely distributed in the central nervous system, where they play a role in the neural control of the cranial circulation and endogenous pain control system. The pathophysiology of migraine involves interaction between these central pathways and cranial blood vessels. It is probable that many prophylactic agents exert their action by central 5-HT2 antagonism, whereas termination of an established attack of migraine depends upon constriction of cranial vessels mediated by 5-HT1 receptors.