We have identified all currently sequenced members of the urea transporter (UT) family (TC #1.A.28). Homologues occur exclusively in vertebrate animals and bacteria but not in other eukaryotic kingdoms or archaea. Sequence, structural, and phylogenetic analyses reveal conserved regions and residues and suggest that a primordial 5 transmembrane helical segment (TMS)-encoding genetic element duplicated to give a 10 TMS-encoding element early during evolutionary history, at about the time when eukaryotes diverged from prokaryotes. Two well-conserved, strongly amphipathic, putative alpha-helices that precede both 5 TMS repeat elements are predicted to be of structural, functional, or biogenic significance. A second duplication event (or a gene fusion event) occurred during development of the vertebrate lineage, giving rise to 20 TMS mammalian homologues. The results suggest that vertebrates acquired UT genetic information from bacteria only once and that all current orthologues and paralogues in the animal kingdom arose from this one primordial system.