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Mechanisms that regulate endolymphatic pH are unknown. It has long been recognized that, because of the large positive endolymphatic potential in the cochlea, a passive movement of protons would be directed out of endolymph leading to endolymphatic alkalization. However, endolymphatic pH is close to that of blood, suggesting that H⁺ is being secreted into endolymph. Since the kidney and the inner ear are both actively engaged in fluid and electrolyte regulation, we attempted to determine whether proteins responsible for acid secretion in the kidney also exist in the guinea pig inner ear. To that end, a monoclonal antibody against a 31 kDa subunit of a vacuolar vH⁺ATPase and a polyclonal, affinity purified antibody against the AE2 Cl ⁻HCO ₃⁻ exchanger (which can also recognize AEI under some conditions) were used. In the cochlea, the strongest immunoreactivity for the vH⁺ATPase was found in apical …