Background: Macrophage migration inhibitory factor and mannose-binding lectin-2 play important roles in the pathogenesis of several acute and chronic inflammatory/autoimmune disorders. The aim of the study was to investigate any possible association between migration inhibitory factor and mannose-binding lectin-2 gene polymorphisms and acute rheumatic fever in children. Material and methods: A total of 38 unrelated children with acute rheumatic fever and 40 age- and sex-matched healthy controls were analysed for codon 54 A/B polymorphism in mannose-binding lectin-2 gene and -173 G/C polymorphism in migration inhibitory factor gene by using the polymerase chain reaction method. Results: Frequency of BB genotype of mannose-binding lectin-2 gene was higher in the patient group. Interestingly, children with acute rheumatic fever with AA genotype tended to have chorea compared with children with BB genotype. There was a statistically significant increase in frequency of the migration inhibitory factor -173 CC genotype in patients compared with the control subjects. Conclusion: The present study is the first to investigate the mannose-binding lectin-2gene polymorphism in children with acute rheumatic fever. BB genotype of mannose-binding lectin-2 (codon 54) and CC genotype of migration inhibitory factor (-173) may have a role in the immunoinflammatory process of acute rheumatic fever.