We have refined and extended the map of the distal half of the human major histocompatibility complex. The map is continuous from HLA-E to 1000 kb telomeric of HLA-F and includes six new markers and genes. In addition, the corresponding sequences that were not previously mapped in the mouse genome have been located. The human and the mouse organizations have therefore been compared. This comparison allows us to demonstrate that the structure of the distal part of the MHC is similar in the two species. In addition, this comparison shows the presence of a breakpoint of synteny telomeric of the distal part of the H-2 region. Indeed, the region telomeric of HLA in human is found on a chromosome different from that carrying H-2 in mouse. The mapping analysis of paralogous genes (structurally related genes) around the breakpoint shows that the human organization probably represents the putative human/mouse ancestral one. This evolutionary breakpoint was precisely mapped in human, and the surrounding region was cloned into yeast artificial chromosomes. Finally, we show that the region found around the breakpoint was involved several times in chromosome recombinations in the mouse lineage, as it seems to correspond also to the t-complex distal inversion point.