X-inactivation is the process which allows equalization of the dosage of X chromosomal genes between males and females. A specific region of the X chromosome, called the X-inactivation centre (XIC), is thought to have a key role in regulating this process. A gene, XIST, has been identified which maps to the XIC and so far has the unique property of being expressed exclusively from the inactive X chromosome. Although XIST is a good candidate for a gene involved in regulating X-inactivation there is as yet no formal proof it has such a role. Here we describe another gene, Cdx4, a member of the caudal-related family of homeobox genes, which is located within the minimal region assigned to XIC in humans. Furthermore, this gene is the closest known gene to XIST in both mouse and human. Unlike Xist, Cdx4 appears to be normally X-inactivated in mice. Although it is not clear whether the location of this gene within the XIC region is of any significance in X-inactivation, the isolation of the gene will allow further definition of the region of inactive X-specific expression surrounding XIST.