Abstract Although several genes for mental retardation and epilepsy, including double cortex/X-linked lissencephaly ( DC/XLIS), have been localized to Xq21.3–q23, there has been no complete physical map of this region available. We constructed a YAC/STS contig map by initiating two yeast artificial chromosome (YAC) walks from the markers that flanked the DC/XLIScandidate gene region. We report an approximately 4-Mb contig extending from DXS287to DXS8088,encompassing DXS1072and DXS1059,and composed of 52 YACs identified with 15 previously published STSs and 19 novel YAC-end STSs. This contig also contains two brain-specific genes, doublecortin(HGMW-approved symbol DCX), responsible for DC/XLIS,and PAK3,which may be responsible for neurological diseases localized to this region. The new contig extends and incorporates several previously published contigs, providing a total overlapping contig extending approximately 34 Mb from DXS441in Xq13.1 to DXS8088in Xq23.