We present the first identification of proteins of the anion exchanger (AE) gene family expressed in human brain. Expression was established by the reverse transcriptase-polymerase chain reaction (RT-PCR), performed on RNA isolated from frontal cortex tissue. The erythroid form AE1, the major non-erythroid form AE2, and a novel member of the AE family, which we named AE0, were identified. Immunohistochemical analysis revealed the highest expression of these proteins in large pyramidal neurons in the frontal cortex and hippocampus. The sequence of the membrane domain of AE0 is identical to that of the major erythroid species AE1, except for the third extracellular loop, which contains a 25 amino acid insertion. This insertion is identical to a sequence in the third extracellular loop of AE2. Expression of AE0 is not restricted to brain tissue, since we could also detect AE0-mRNA in T-lymphocytes and reticulocytes. Chromosomal mapping indicates that the AE0 gene is most likely located on human chromosome 22. We did not find any indications for qualitative changes in AE1, AE2, or AE0 in Alzheimer brain tissue.