Tumor necrosis factor alpha (TNFalpha) is a potent inflammatory cytokine. In human, the TNFalpha gene is located within the highly polymorphic major histocompatibility complex (MHC) region on chromosome 6p21.3. TNF gene cluster contains many polymorphisms including microsatellites and single nucleotide polymorphisms (SNPs). Many of these polymorphisms were found to be in linkage disequilibrium with HLA class I and II alleles. Some of the TNFalpha gene polymorphisms were found to influence TNFalpha production in vitro, for example the -308 SNP. Many studies have shown that this SNP and others within the TNFalpha gene associate with different inflammatory conditions. Whether this phenomenon is due to the direct influence of the SNP in question and/or due to linkage disequilibrium with other polymorphisms within the TNFalpha gene or the HLA system is still controversial.