Urea transporters encoded by the UT-A gene play fundamental roles in the kidney and possibly other tissues. Knowledge of the genomic organization of the mouse, rat and human UT-A genes has enabled the engineering of transgenic and knockout animals and these have helped refine our understanding of the role of UT-A proteins. This review summarizes the published work that has accrued on the structure and regulation of these genes. It also documents a novel cDNA, human UT-A3, which has enabled a major refinement of the human UT-A gene structure. This and other information contained in this review should prove useful for future comparative genomic analysis, studies addressing gene regulation and for the engineering of transgenic and knockout animal strains.