It has been suggested that magnesium (Mg) may play a role in the pathogenesis of headaches. Serum and intracellular measurements of Mg in headache patients have produced inconsistent results. The recent development of an ion-selective electrode for Mg2+ allowed precise measurement of serum ionized magnesium (IMg2+) in patients with various headache syndromes. Low serum IMg2+ and a high ICa2+/IMg2+ ratio were found in 42% of patients having an attack of migraine, but only in 23% of patients with a severe continuous headache. Total serum Mg was normal in both groups of patients. However, in patients with low serum IMg2+ total serum Mg was lower than in patients with normal serum IMg2+. These results are compatible with the serotonin and vascular concepts of migraine pathogenesis. Low IMg2+ and a high ICa2+/IMg2+ would result in cerebral vasospasm and reduced blood flow in the brain. The activity of serotonin receptors can also be affected by changes in IMg2+ levels. The finding of a difference in IMg2+ levels in two different headache types suggests a possible novel classification of headaches and that migraine patients with a low serum IMg2+ or a high ICa2+/IMg2+ ratio may benefit from Mg supplementation.