Although histamine has been suggested as a possible vasoactive mediator in the pathogenesis of migraine, the mechanism of histamine release and its exact role in the pathophysiology of migraine is unclear. The spontaneous release of histamine from plasma-free leucocyte suspensions was examined in 9 patients with 5 types of migraine. The patients were 7 to 46 years of age and had migraine for 1 to 17 years. All were symptom-free for at least one week before the study and none had a history of food allergy. Nine control individuals (2–32 years old) had other types of headache, seizure disorders, or other medical problems.The mean spontaneous histamine release (SHR) was 73.7% ± 14.88 by leucocytes from migraine patients and 22.8% ± 11.67 in control patients (p<0.001). These preliminary findings indicate that the SHR assay may be a useful clinical marker for migraine and may provide additional information on the pathogenesis of migraine.