A large number of diseases are associated with the human major histocompatibility (HLA) complex located in 6p21.3. The underlying defect of most of these has not yet been determined even after detailed analysis of the HLA region. Due to the extended haplotypes found in this area, several of the HLA-linked disease genes may be located also telomeric of the class I region. In order to analyse the area covering the 4 megabases directly telomeric of HLA-F in close detail, we have generated 50 new markers. These and other markers have been used to establish a SalI restriction map from 46 YACs. A subset of 42 markers was applied to construct a genomic long range restriction map from an HLA-A2/B13 haplotype. Both maps have been compared revealing the presence of additional 150 kb in the HLA-A2 haplotype close to the RFP locus. Additionally, 47 PACs have been selected mapping to this region and grouped into 7 contigs. Sequencing of these PAC contigs has already been initiated.