The loci determining polymorphism of genes involved in the immune response feature prominently in the susceptibility to autoimmune thyroid disease. However, disease phenotypes do not segregate perfectly with the genetic markers. The interaction between the influence of these loci on susceptibility is complex, and when taken in the context of the multilayered, multidirectional workings of the immune network and that of as-yet-unspecified environmental factors, our difficulty in predicting the susceptible phenotypes is not surprising.