Oxygen inhalation was early advocated as a treatment for migraine headache. It has been theorized that the efficacy of raising blood oxygen levels in vascular headache is mediated by vasoconstriction and metabolic effects. Hyperbaric oxygen can provide a much greater level of blood oxygenation than normobaric oxygen, and in recent studies it has been used in the treatment of cluster headache. The purpose of this study was to compare the effects of hyperbaric oxygen and normobaric oxygen in migraine. Twenty migraineurs were divided randomly into two groups and studied in a hyperbaric chamber during a typical headache attack. Global headache severity was measured by a verbal descriptor scale before and after exposure to oxygen. One group received 100% oxygen at I atmosphere of pressure (normobaric) while the other received 100% oxygen at 2 atmospheres of pressure (hyper-baric). One of the 10 patients in the normobaric group achieved significant relief of headache symptoms, while 9 of 10 in the hyperbaric group found relief. Based on a chi-square test, this difference is significant at the P<.005 level. Those patients who did not find significant relief from normobaric oxygen were given hyperbaric oxygen as above. All nine found significant relief. The results suggest that hyperbaric (but not normobaric) oxygen may be useful in the abortive management of migraine headache. Possibilities for the mechanism of this effect, in addition to vasoconstriction, include an increase in the rate of energy-producing and neurotransmitter-related metabolic reactions in the brain which require molecular oxygen.