Haplotypes spanning the tumor necrosis factor (TNF) gene block in the central major histocompatibility complex were defined in a Southern African population using 31 single-nucleotide polymorphisms. Twenty haplotypes accounted for 91.8% of the cohort. The haplotypes matched those described previously in Caucasian and Asian populations, supporting the hypothesis that TNF block haplotypes are ancient and highly conserved. They are presented here as a tool for disease-association studies.Genes and Immunity advance online publication, 14 March 2013; doi:10.1038/gene.2013.8.