The electroneutral Na-HCO₃ cotransporter NBCn1 (SLC4A7) is located at the basolateral membrane of the thick ascending limb, where the 1:1 uptake of Na⁺ and HCO₃^– into the cell neutralizes the intracellular acid load caused by the apical uptake of NH₄⁺. NBCn1 also plays an important role in intracellular pH regulation in vascular smooth muscle cells (see Romero et al. 2004 for review). Human NBCn1 has an unusually long N terminus (Nt) that is about half the length of the entire protein, and is reported to begin with the amino-acid sequence Met-Glu-Arg-Phe, MERF. The unusual length of the Nt is due to a unique 124-residue cassette (Exon 7) and a 13-residue cassette A at the extreme end of exon 6. Rat NBCn1 has been reported to begin with a different Nt (Met-Glu-Ala-Asp, MEAD), and may have exon 7 spliced in or out as a cassette. (Rat NBCn1 also contains a cassette B, which consists of 36 residues in the C terminus.) The different Nt of the human NBCn1-A MERF vs the rat NBCn1-B through -E MEAD have been thought to represent species differences. However, we now report four new full-length human cDNA clones, two beginning with MERF and two beginning with MEAD. The two beginning with MERF were found in skeletal muscle and kidney but not liver libraries; they differ in a potential polymorphism in exon 7. The two beginning with MEAD were found in skeletal muscle, liver, kidney and heart libraries; they differ in the presence vs absence of exon 7. Examination of the human genome indicates that MERF and MEAD indeed represent alterative N-termini originating from different exons, exon 1 in the case of MERF (5 kb upstream from exon 2 and encoding 11 amino acids) and what we shall term exon 0 in the case of MEAD (30 kb upstream from exon 2 and encoding a different 16 amino acids). The same holds true for the mouse genome, where previously only MEAD was though to exist. To date, NBCn1 is the most diverse Na⁺-coupled SLC4, with at least three cassettes that may be spliced in or out, as well as two alternative N termini. Our results could impact our understanding of NBCn1 physiology in the following ways: (1) detection of NBCn1 using only an antibody directed against MERF would fail to detect NBCn1 splice variants beginning with MEAD. Although one might contemplate developing an antibody against MEAD, MEAD closely resembles the Nt of another SLC4 family member, NCBE (SLC4A10). (2) Different tissues, as we have seen, may exhibit differential expression of the new NBCn1 splice variants. (3) The choice of N termini and the presence or absence of particular cassettes presumably affects NBCn1 physiology via binding partners and/or effects on the function of the transmembrane domain.