Incontinentia pigmenti (IP) is an X-linked dominant disorder of neuroectodermal development. Based on the observation of six unrelated females with clinical features of nonfamilial IP with constitutional de novo reciprocal X;autosome translocations, a putative incontinentia pigmenti type 1 locus (IP1; MIM No. 308300) was localized to region Xp11.21. Using available regional DNA markers, we constructed a yeast artificial chromosome (YAC) contig that contained 1.2 Mb of distal Xp11.21 and spanned two IP1 X-chromosomal breakpoints. This contig was used to generate a detailed molecular map of the region and identify three regional CpG islands. YAC-derived cosmids were used to clone and map the IP1 breakpoints to a 180-kb interval that was flanked by DNA markers DXS705 and DXS741. The physical map and genomic clones should facilitate the isolation and characterization of transcripts associated with the IP1 translocation breakpoints.