The reported linkage between bipolar disorder and a large pericentric portion of chromosome 18 has been replicated in an independent study. Further examination of this region showed that 18p11.2 had the greatest allele sharing in our pedigrees and increased sharing in other independently ascertained pedigree series permitting refinement of the region of significance. To facilitate positional cloning of a susceptibility gene, we used a combination of mapping reagents, including a subchromosomal somatic cell hybrid panel, a contig of clones in yeast artificial chromosomes (YAC), and a radiation hybrid (RH) panel, to construct a high resolution physical map of the region including sequence tag sites (STSs) and expressed sequence tags (ESTs). This approach generated the interlocus distance and order of 15 STSs and 16 ESTs including four novel transcripts, with an average of approximately 200 kb between loci, over a approximately 6-Mb region. This high resolution integrated map will be an important tool in providing loci for contig construction, and positional candidates for mutation screening.