In pure phospholipid vesicles, the conductivity of H+/OH- ions exceeds that for other simple inorganic ions. Protons achieve electrochemical equilibrium across egg phosphatidylcholine vesicles within tens of minutes. When pH gradients are established across vesicles, transmembrane potentials develop. Conversely, the establishment of transmembrane potentials leads to the formation of pH gradients. When the phenomenological permeability of H+/OH- ions in vesicles is estimated, values are obtained that are much greater (six orders of magnitude larger) than those for Na+ or K+. A wide range in the values for this permeability has been reported; however, much of the discrepancy can be attributed to differences in the vesicle systems and experimental conditions. The H+/OH- current appears to be modulated by changes in membrane dielectric constant. However, the dependence of this current on the pH gradient and on the membrane voltage argues against simple diffusion mechanisms as the source of the H+/OH- current. In addition, in vesicle systems the H+/OH- current shows a surprising invariance to changes in the membrane dipole potential, an observation that argues against the role of simple carriers for H+ and OH- ions.