Retinoid-X receptors (RXRs) are a subfamily of the steroid/thyroid nuclear receptor superfamily. There are three RXR genes: alpha, beta, and gamma, each with a distinct expression pattern and chromosomal location. In this study we describe the genomic organization of the mouse RXR gamma gene, identify a second mouse (m) RXR gamma isoform, and map the exons of the two mRXR gamma isoforms on the gene. The new mRXR gamma isoform, called gamma 2, has a unique 5'-untranslated region, and is expressed highly in both cardiac and skeletal muscles, but very little in the liver, while the mRXR gamma 1 is expressed in the brain and muscle. The gamma 2 isoform is also a functional receptor and can transactivate the retinoid response elements of the apolipoprotein-AI and cellular retinol-binding protein-II genes. The mRXR gamma gene spans at least 50 kilobases of DNA on mouse chromosome 1 and has nine introns ranging from 107 basepairs to more than 30 kilobases. From the genomic separation of the two unique 5'-ends of the mRXR gamma isoforms, it is suggested that this gene may have two promoters, similar to those described for the three RAR genes. The results of this study along with those of previously published studies suggest that there may be more than two isoforms of mRXR gamma.