Type 1 (insulin-dependent) diabetes, T1DM, is the result of an immune-mediated destruction of the pancreatic beta cells dependent mainly on T helper cells and macrophages. Interleukin-18 (IL-18) is a proinflammatory cytokine produced mainly by macrophages. IL-18 is capable of inducing T lymphocyte synthesis of IFNgamma, thereby skewing the T helper response toward a T helper type 1 (Th1) profile. IL-18 binding protein (IL18BP) neutralizes IL-18 and leads to a reduced Th1 response. Polymorphisms in IL18BP may affect the activity of IL-18 and the magnitude of the Th1 response and may play a role in the pathogenesis of T1DM. The aim of the study was therefore to identify polymorphisms in IL18BP and to test these for association with T1DM. We evaluated the human IL18BP gene on chromosome 11q13 as a candidate susceptibility gene for T1DM and scanned the entire IL18BP (promoter, exons 1-6, and 3'UTR) for polymorphisms using single-strand conformational polymorphism analysis and direct sequencing. We identified a total of 11 polymorphisms, all having allele frequencies ranging between 0.05 and 0.10. Four were in the 5'UTR: -257G-->T, -78C-->T, -65G-->A, and -59A-->G. Three were in intron 3: IVS3+140A-->C, IVS4-147G-->T, and IVS4-59G-->T. The last four, 38*A-->T, 48*T-->A, 388*C-->G, and 440*_441*insG, were in the 3'UTR of IL18BP. However, none of these were frequent enough to permit association studies in T1DM and we conclude that IL18BP does not contribute to the overall genetic susceptibility to type 1 diabetes.