Retinoid X receptors (RXRs) are members of the steroid/thyroid hormone receptor superfamily which, along with retinoic acid receptors (RARs), mediate the biological effects of retinoids. These effects include the regulation of many aspects of embryonic development, reproductive and visual function, and the maintenance of epithelial homeostasis throughout life. The genes for three distinct retinoid X receptors, RXR alpha, beta, and gamma, have been localized to separate chromosomes, In order to determine the organization of the human RXR alpha gene, we have isolated a clone containing the majority of the gene from a human genomic bacterial artificial chromosome (BAC) library and generated a physical map. The gene spans over 40 kilobases in size and contains at least 10 exons. Comparison with mapped portions of the mouse RXR alpha gene indicates highly conserved intron-exon positioning. These results provide information necessary to generate constructs for targeting the RXR alpha gene in human cell lines, which may eventually lead to an understanding of the function of RXR alpha in human cancer.