The appearance of autoantibodies is a common characteristic of ulcerative colitis (UC). Specifically, anti-neutrophil cytoplasmic antibodies (ANCA) are the most prevalent in this disease and their synthesis may be genetically conditioned. The aim of the present study was to test the influence on appearance of autoantibodies of IL-10 and TNFalpha genes promoter polymorphisms, which control cytokine levels. Genetic polymorphisms of TNFalpha (-308 G/A) and IL-10 (-1082 G/A) and ANCA and anti-goblet cells antibodies (GAB) presence were determined in 99 UC patients. The -308A* allele and -308AA/AGTNFalpha genotypes (high producer), clearly correlated with ANCA positivity (p = 0.004 and p = 0.007, respectively). Additionally, homozygous carriage of the -1082A*IL-10 allele (low producer) significantly associated with ANCA presence (p = 0.007). Furthermore, combination of both genotypes (low IL-10/high TNFalpha producer genotype) had a greater influence on ANCA positivity than each individual genotype (p = 0.008). ANCA production in UC thus appears to be conditioned by IL-10 and TNFalpha genotypes.