Serum complement components and immunoglobulins were measured in migraineurs. Patients were assigned to two groups: Group I (prodromal migraineurs), Group 2 (non-prodromal). This group was subdivided into Group 2A (common) and Group 2B (with focal neurologic symptoms commencing after headache onset). In the immunoglobulin study: Group 1 had an elevated IgA level, Group 2A had elevated IgG, IgA and Group 2B elevated IgG, IgA and IgM when compared with appropriate controls. The IgM in group 2B was significantly higher than in Groups I and 2A, supporting the division into two groups of patients with focal neurologic symptoms. The complement study compared patients during headache and when headache-free. The “in headache” patients were further subdivided into early and late groups. The complement results are from patients in Group 2 only. During headache, samples were obtained from 18 migraineurs. In 9 patients headache-free specimens were collected enabling paired analysis of results. Reductions in levels of C4 and C5 in the paired study, lower levels of C4, C1s and C1(1) during early headache in the unpaired study are evidence of complement activation associated with migraine. Demonstration of complement breakdown products in three patients at least three hours before headache onset, and absence of difference in component levels between headache-free and late headache migraineurs indicates complement activation of short duration. Elevated immunoglobulin levels and complement activation suggest a late-onset immune reaction of short duration. Such a mechanism provides an explanation of many of the features of non-prodromal migraine; platelet release of serotonin, basophil and mast cell degranulation, increased whole blood histamine during an attack, fluid retention, increased thrombotic tendency and increased CSF lactate and GABA.