This paper reports the isolation and characterization of three distinct RXR (retinoid X receptor) genes in mice, encoding RXRα, β, and γ proteins. These receptors are closely related in their DNA- and ligand-binding domains but differ significantly in their amino-terminal regions. The study demonstrates that 9-cis retinoic acid (9-cis RA) is a potent ligand for all three RXR subtypes, with up to 40-fold higher potency than all-trans retinoic acid (all-trans RA). Trans-activation assays show that 9-cis RA is more potent than all-trans RA in activating RXR target genes. Northern blot and in situ hybridization analyses reveal a broad spectrum of RXR expression patterns during development and in adult tissues, with unique and overlapping patterns for each receptor subtype. The RXRs are expressed in various tissues, including the liver, kidney, and brain, and show differential expression in specific organs. The RXRγ receptor is particularly restricted, with high expression in the corpus striatum and pituitary. The study suggests that the RXR family plays critical roles in diverse aspects of development, from embryo implantation to organogenesis and central nervous system differentiation, as well as in adult physiology. The discovery of three RXR subtypes and their ligand 9-cis RA defines a new retinoid signaling pathway, highlighting the complexity and diversity of retinoid actions in vertebrate development and physiology.This paper reports the isolation and characterization of three distinct RXR (retinoid X receptor) genes in mice, encoding RXRα, β, and γ proteins. These receptors are closely related in their DNA- and ligand-binding domains but differ significantly in their amino-terminal regions. The study demonstrates that 9-cis retinoic acid (9-cis RA) is a potent ligand for all three RXR subtypes, with up to 40-fold higher potency than all-trans retinoic acid (all-trans RA). Trans-activation assays show that 9-cis RA is more potent than all-trans RA in activating RXR target genes. Northern blot and in situ hybridization analyses reveal a broad spectrum of RXR expression patterns during development and in adult tissues, with unique and overlapping patterns for each receptor subtype. The RXRs are expressed in various tissues, including the liver, kidney, and brain, and show differential expression in specific organs. The RXRγ receptor is particularly restricted, with high expression in the corpus striatum and pituitary. The study suggests that the RXR family plays critical roles in diverse aspects of development, from embryo implantation to organogenesis and central nervous system differentiation, as well as in adult physiology. The discovery of three RXR subtypes and their ligand 9-cis RA defines a new retinoid signaling pathway, highlighting the complexity and diversity of retinoid actions in vertebrate development and physiology.