Using primers against conserved regions of mammalian SGLTs cDNAs were cloned from the kidney of spiny dogfish shark (Squalus acanthias). Based on comparison of amino acid sequence, membrane topology, putative glycosylation and phosphorylation sites the cDNA could be shown to belong to the family of sglt genes. Indeed, sodium dependent D-glucose uptake could be demonstrated after expression of the gene in Xenopus laevis oocytes. In a dendrogram the SGLT from shark kidney has a high homology to the mammalian SGLT2. Computer analysis revealed that the elasmobranch protein is most similar to the mammalian proteins in the transmembrane regions and contains already all the amino acids identified to be functionally important, suggesting early conservation during evolution. Extramembranous loops show larger variations. This holds especially for loop 13, which has been implied as a phlorizin-binding domain. Antibodies were generated and the intrarenal distribution of the SGLT was studied in cryosections. In parallel the nephron segments were identified by specific lectins. Positive immunoreactions were found in the proximal tubule in the early parts PIa and PIb and the late segment PIIb. The large PIIa segment of the proximal tubule showed no reaction. In contrast to the mammalian kidney also the late distal tubule, the collecting tubule and the collecting ducts showed immunoreactivity. The molecular information confirms previous vesicle studies in which a low affinity SGLT with a low stoichometry has been observed and supports the notion of a similarity of the shark kidney SGLT to the mammalian SGLT2. Despite its presence in the late parts of the nephron, the absence of SGLT in the major part of the proximal tubule, the relatively low affinity, and in particular the low stoichiometry might explain the lack of a T_m for D-glucose in the shark kidney.