Migraine without aura (MO) and migraine with aura (MA) are disorders involving multiple environmental and genetic factors. The A/G polymorphism located within exon 1 of the gene encoding the cytotoxic T lymphocyte antigen 4 (CTLA-4) is associated with several HLA-associated multifactorial diseases. The CTLA-4 family shows a negative control on T-cell proliferation and cytokine production (TNF-alpha and IL-10). In the present study we investigated the contribution of the candidate gene CTLA-4 in migraine pathophysiology. Included in the study were 96 MO and 39 MA migraine patients and 106 healthy individuals as control group. The results showed no statistical difference of allele frequencies between patient group and control group. These results would indicate no association between MA and MO migraine and CTLA-4 polymorphism, excluding any possible role of the CTLA-4 gene as a genetic factor determining susceptibility to migraine.