Killer cell immunoglobulin-like receptors (KIR) regulate the effector function of natural killer (NK) cells and the subset of T cells with memory phenotype. The number and type of genes that encode KIR receptors substantially varied between individuals and between populations. Specific KIR receptors are known to be associated with certain diseases. The present study was undertaken to investigate if any specific KIR gene(s) is associated with the susceptibility to Hashimoto's thyroiditis (HT), an inflammatory disease characterized by lymphocytic infiltration of the thyroid gland and the presence of autoantibodies directed against thyroglobulin and/or thyroid peroxidase. DNA from 118 patients with HT and 120 healthy controls was characterized for the presence and absence of 11 variable KIR genes using a gene-specific PCR typing system. Although no significant difference in the frequency of individual KIR genes between patients and controls was detected, more patients carry the six activating KIR genes compared with the control group (11.8 vs. 4.1 %, p = 0.032, OR = 3.09, 95 % CI 1.07-8.89). The data suggest that augmented signals from multiple activating KIR receptors might exacerbate the activation of NK cells and T cell subsets against self-antigens, thus contributing to the pathogenesis of HT.