In XX female mammals, inactivation of one X chromosome during development equalises the levels of X-linked gene products in females with those in males. Expression of the Xist gene from one of the two X chromosomes produces a non-coding RNA that coats and silences the chromosome from which it is transcribed. But how does Xist RNA induce chromosome silencing? XistIVS, an Xist mutant generated in mice by gene targeting, may help to answer this question, suggest Takashi Sado and co-workers (see p. 2649). In embryos carrying the XistIVS allele, they report, XistIVS is differentially upregulated, and its mutated transcript coats the X chromosome in cis in embryonic and extra-embryonic tissues, but X-inactivation is incomplete. This partial X-inactivation seems to be unstable, and the mutated X chromosome is reactivated in some extra-embryonic tissues and possibly in early epiblastic cells, suggesting that the RNA encoded by XistIVS is dysfunctional. Further studies of this unique mutation could thus reveal exactly how Xist RNA induces chromosome silencing.