The role of antihistamine therapy in vascular headaches. Migraine (vascular) headache is a complex syndrome that involves vascular hyperreactivity. The functions of systemic mediators in migraine are not fully understood. It is unclear which mediators provoke this probably atopic disorder and which represent an attempt to correct an imbalance. However, it has been demonstrated fairly conclusively that increased histamine levels correlate with migraine attacks in susceptible persons. Recent studies showing that histamine seems to have many different receptors and to adopt different conformations for different receptors may serve as a useful guide to future scientific investigation. Further impetus may come from ongoing studies of H3 histamine receptors, which indicate that H3 agonists offer promise as prophylactic agents for people who suffer from vascular headaches. 