Histones are basic proteins which are responsible for the assembly and maintenance of the nucleosomal structure within the chromosomal fiber in eukaryotes. Two clusters of these genes have previously been mapped to the region 6p21.1-p22.2. We describe here a radiation hybrid map, a long range restriction map and a YAC contig covering and linking these two clusters and giving the precise localisation with respect to the HLA complex. The large cluster contains five H1 histone genes in the 6p22.2 region, the smaller only one, H1F5 (H1.5), in 6p22.1. In both clusters, each H1 locus is accompanied by several core histone genes. The large cluster has additionally been covered by a sequence ready PAC contig and three probably unrelated genes (TRMI2, BTN and SSADH) have been accurately localized within the 6p22.2-p22.1 region.