The human major histocompatibility complex (MHC), on the short arm of chromosome 6, represents one of the most extensively characterised regions of the human genome. This -4 Mb segment of DNA contains genes encoding the polymorphic MHC class I and class I1 molecules which are involved in antigen presentation during an immune response. Recently the whole of the MHC has been cloned in cosmids and/or yeast artificial chromosomes (YACs) and large portions have been characterised for the presence of novel genes. Many unrelated genes, both housekeeping and tissue specific, have been identified and the gene density in some regions is now approaching one gene every few kilobases. Some of the novel genes encode proteins involved in the intracellular processing and transport of antigens that are presented by MHC class I molecules. Others, however, have no obvious role in the immune response. The MHC is located in the chromosome band 6p21.3 which is a Giemsa (G)- light band. The detection of such a large number of functional genes (at least 70) in this region is compatible with the idea that both housekeeping and tissue-specific genes are localised predominantly in G-light bands. 111 regions are marked. The genes in the class I1 subregions (DP, DNA, DOB, DQ and DR) are represented by bars. The locations of the genes encoding the class I histocompatibility antigens (HLA-A, -B and -C): the class I-like gcncs (HLA and) and the cdal2 gene are also shown. In the class 111 region the complement genes (C4, C2 and factor B) and the TNF genes arc marked.