Abstract To assess the role of interleukin-6 (IL-6) in migraine, we analyzed the −174 G/C IL-6 gene polymorphism in 268 patients with migraine and 305 controls. No significant difference in the distribution of IL-6 genotypes ( χ 2=0.601, P=0.74) and allelic frequencies ( χ 2=0.024, P=0.876) was found. When patients were subdivided into subgroups (migraine with aura, migraine without aura and mixed headaches), IL-6 alleles were similarly distributed. Comparison of the clinical features of the disease with the −174 G/C IL-6 genotypes showed no significant difference. In conclusion, we found no significant association between the −174 G/C IL-6 polymorphism and the occurrence or the clinical features of migraine.