Autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and autoimmune hypothyroidism (AH), are inherited as complex traits. Among the genes contributing to AITDs susceptibility are genes of the IL-1 family. IL-1 regulates T and B lymphocyte maturation, including the induction of several cytokines and cytokine receptors. Therefore, disturbances of this balance may not only play a role in inflammation but also in the pathogenesis of autoimmunity. In order to investigate genetic association of IL-1 gene polymorphisms with AITDs, we performed both a familial study in a large Tunisian pedigree with high prevalence of AITDs (64 patients and 176 controls), and a case-control study (131 GD unrelated patients and 225 healthy controls). PCR and PCR-RFLP methods were used to analyse respectively a VNTR in the IL-1RN gene and three SNPs in both IL-1B genes (-511 C/T and +3954 C/T) and IL-1A (-889 C/T). The family-based association study showed an association of the IL-1B+3954 C/T polymorphism (p = 0.02) and two haplotypes IL-1RN*3/C/T/T and IL-1RN*1/C/T/T (p = 0.009 and p = 0.047 respectively) with AITDs. The case-control study is the first study revealing a significant association of the IL-1A-889 C/T polymorphism (chi2 = 10.23; p = 0.0014) with susceptibility to GD. Our data suggest that the IL-1 gene cluster may harbour susceptibility genes for AITDs and GD pathogenesis in the Tunisian population.