We studied a group of migraine patients for circulating immune complexes, lymphocyte subpopulations, IgG4 and anti-IgG antibodies, before, after 4 hours and after 72 hours a specific challenge test. We found an increased incidence of circulating immune complexes. Total T cells showed a marked increase after challenge test. The most important finding was the presence of T-activated cells. Also K and NK cells showed an early increase after the challenge. In commenting the outcomes of this investigation, it must be stressed that the evidence of an early lymphocyte activation after the challenge test indicates an involvement of interleukin-2 related receptor in food-induced migraine. The results have reinforced the idea of immune mechanism involvement in food-induced migraine, but it seems to be localized at different step from that until now hypothesized, with the involvement of the complex cytokines network.