The presence of carbonic anhydrase (CA) activity in the neural retina has been known for several decades. CA-II, a soluble cytoplasmic isoform expressed by Müller cells and a subset of amacrine cells, was thought to be the sole source of CA activity in the neural retina. However, CA-II deficient mice retain CA activity in the neural retina, which implies that another isoform must be present in that tissue. Recently CA-XIV, an integral membrane protein, was cloned and characterized. We, therefore, sought to determine whether CA-XIV is expressed in the neural retina, and hence is responsible for the CA activity observed in CA-II null animals. Immunohistochemical analyses of histological sections from CA-II null, CA-XIV null, and control mice were performed to localize the CA-XIV isoform, as well as other known retinal markers. Immunoblotting and real-time RT-PCR analyses were also performed to test for CA-XIV expression in retina and other mouse tissues. We determined herein that CA-XIV, a approximately 45kDa membrane protein, is expressed in retina, as it is in kidney. In the retina, CA-XIV is expressed on the plasma membrane of Müller cells. CA-XIV is also found on both the apical and basal membranes of the retinal pigmented epithelium. The data presented here indicate that like CA-II, CA-XIV is highly expressed in the neural retina and, like CA-II, more specifically by the Müller cells. The cellular compartmentalization of the two isoforms in the Müller cell-one cytoplasmic and the other on the plasma membrane-suggest that the two enzymes have specific and unique functions. Future studies will be necessary to assign functions to CA-II and CA-XIV in the mouse neural retina.