Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) are cytokines with a wide range of inflammatory and immunomodulatory activities. Type 1 diabetes is an autoimmune disease characterized by destruction of insulin-producing pancreatic beta cells. The aim of the present study was to evaluate the association of polymorphisms in the TNF/LTA gene region with susceptibility to type 1 diabetes. We investigated 11 TNF/LTA tag polymorphisms, designed to capture the majority of common variation in the region, in 160 trio families from South Croatia. We observed overtransmission of alleles from parents to affected child at five variants: (rs909253, allele C, p = 1.2x10(-4); rs1041981, allele A, p = 1.1x10(-4); rs1800629 (G-308A), allele A, p = 1.2x10(-4); rs361525 (G-238A), allele G, p = 8.2x10(-3) and rs3093668, allele G, p = 0.014). We also identified overtransmission of the rs1800629(G-308A)-rs361525(G-238A) A-G haplotype, p = 2.384x10(-5). The present study found an association of the TNF/LTA gene region with type 1 diabetes. A careful assessment of TNF/LTA variants adjusted for linkage disequilibrium with HLA loci is needed to further clarify the role of these genes in type 1 diabetes susceptibility in the population of South Croatia.