BACKGROUND: Various polymorphisms occur in cytokine genes involved in inflammatory processes in Graves' ophthalmopathy (GO). Anti-inflammatory cytokines such as transforming growth factor- beta (TGF-beta), interleukin-10 (IL-10) and interleukin-4 (IL-4) are among those believed to be involved in the disease process. In this study, we investigated the association between 8 polymorphisms within the mentioned cytokines and GO. METHODS: The following polymorphisms were studied in 50 patients with GO, 57 Graves' patients without GO and 140 healthy individuals using polymerase chain reaction with sequence-specific primers: TGF-beta (+869C/T, +915G/C), IL-10 (-1082A/G, -819C/T, -592C/A) and IL-4 (-1098T/G, -590T/C, -33C/T). A corrected p value less than 0.05 was considered statistically significant. RESULTS: The TGF-beta +915C allele (Odds Ratio [OR] = 2.20) and CC genotype (OR = 7.50) as well as +869C allele (OR = 2.21) showed significant correlations with GO. Regarding IL-4 polymorphisms, the -1098G allele (OR = 2.09) and GG genotype (OR = 7.49), and the -33T allele (OR = 2.05) and TT genotype (OR = 4.00) were significantly associated with GO. The IL-10 -819TT genotype (OR = 5.00) was significantly correlated with GO. CONCLUSION: This is the first study to show that polymorphisms in anti-inflammatory cytokine genes are associated with susceptibility to GO.