The Na+/H+ exchangers belong to a family of transport proteins involved in intracellular pH regulation and vectorial sodium transport across various epithelial tissues. We have cloned a unique isoform (NHE-2) by screening a rat intestinal cDNA library utilizing a human NHE-1 fragment. In this report we describe molecular cloning of the human Na+/H+ exchanger (NHE-2, HGMW-approved symbol SLC9A2). The cDNA encodes a protein of 698 amino acid residues. Human NHE-2 is widely distributed in tissues of the gastrointestinal tract, kidney, heart, testes, uterus, and adrenal glands. Hydropathy plot indicates that the translated protein is predicted to have 10 transmembrane domains with three potential N-glycosylation sites and four potential cAMP- and cGMP-dependent protein kinase phosphorylation sites. This cDNA maps the location of the gene encoding NHE-2 to human chromosome 2q11.2.