The recently described retinoid X receptors (RXRs) respond to the novel retinoid 9-cis-retinoic acid and also serve as heterodimeric partners for the vitamin D, thyroid hormone, and retinoic acid receptors (VDR, TR, and RAR, respectively). In this work, we report high-resolution localization of the human RXR genes within cytogenetic bands and also within a standard reference map of cosmid DNA markers on human chromosomes. We have determined the location of the human RXR genes by pairwise hybridization of the RXR cosmids and reference markers, using fluorescence in situ hybridization. We localized (i) RXR alpha (RXRA) to chromosome 9 band q34.3; (ii) RXR beta (RXRB) to chromosome 6 band 21.3; and (iii) RXR gamma (RXRG) to chromosome 1 band q22-q23. Six retinoid-responsive transcription factors have been identified so far, including three retinoic acid receptors in addition to the three RXRs. Interestingly, each of these receptors in human and mouse is encoded by genes located at distinct chromosomal loci and on separate chromosomes. The proximity of RXR genes to loci known to be associated with genetic disorders suggests that their location may be useful in establishing a link between RXRs and certain human diseases.