Passive H+/OH- permeability across epithelial cell membranes is rapid and leads to partial dissipation of H+/OH- gradients produced by H+ pumps and ion gradient-coupled H+/OH- transporters. A heterogeneous set of H+/OH- transport mechanisms exist in biological membranes: lipid solubility/diffusion, protein-mediated transport by specific proteins or by slippage through ion-coupled H+/OH- transporters, and transport at the protein/lipid interface or through protein-dependent defects in the lipid structure. A variety of methods are available to study protein transport mechanisms accurately in cells and biomembrane vesicles including pH electrode recordings, pH-sensitive fluorescent and magnetic resonance probes, and potentiometric probes. In brush border vesicles from the renal proximal tubule, the characteristics of passive H+/OH- permeability are quite similar to those reported for passive H+/OH- permeability through pure lipid bilayers; slippage of protons through the brush border Na+/H+ antiporter or through brush border water channels is minimal. In contrast, passive H+/OH- permeability in brush border vesicles from human placenta is mediated in part by a stilbene-sensitive membrane protein. To demonstrate the physiological significance of passive renal brush border H+/OH- transport, proximal tubule acidification and cell pH regulation mechanisms are modeled mathematically for states of normal and altered H+/OH- permeabilities.