Although migraine affects about 15% of population and many studies have been performed to find the mechanism and a successful management, the physiopathology of migraine is still largely unknown. The possibility of an immunoglobulin E (IgE)-mediated allergic mechanism and the role of histamine remain controversial. The aim of the present study was to evaluate serum total IgE and histamine levels in migraine patients and the influence of allergy on them. Seventy patients (18-58 years) with migraine without aura were divided into two groups according to their history of allergy (60% with and 40% without allergy). Serum samples were collected during fasting without allowing any premedication during the two periods of attack and remission. There was a control group containing 45 healthy volunteers. Serum total IgE and histamine levels were measured by enzyme-linked immunosorbent assay and fluorimetric methods, respectively. Mean and standard errors of serum histamine (ng/ml) and total IgE (IU/ml) levels were found in the control group to be 48.16 +/- 2.70 and 38.31 +/- 3.20, in the migraine with allergy group 159.11 +/- 4.60 and 303.30 +/- 42.50 and in the migraine without allergy group 105.01 +/- 8.50 and 79.07 +/- 2.70, respectively. Total IgE levels in migraine with allergy group were found to be significantly (P < 0.0001) above that in the control and another group, suggesting an influence of an IgE-mediated mechanism on migraine. Although the plasma histamine levels, which were significantly elevated (P < 0.0001) in patients with migraine, both during headache and symptom-free periods, when compared with the control group, indicate that there is an increased susceptibility to histamine in allergic conditions, this molecule has also an unrelated role in migraine. The relationship between allergy and migraine can be based, in part, on an IgE-mediated mechanism, and histamine release plays an important role. Thus, the avoidance of allergic conditions in migraine patients may be a simple, helpful way for prophylaxis or their treatment.