An ATP-dependent proton pump drives epinephrine transport in chromaffin granule ghosts. When ghosts are suspended in a medium free of permeant anions, ATP addition leads to an increase in membrane potential (interior positive) and epinephrine uptake but not to a change in intravesicular pH. Since ATP does not affect the pH gradient, the energy for transport must be drawn from the membrane potential (delta psi), and epinephrine uptake must result in a net efflux of positive charge. This can be achieved by an antiport (exchange diffusion) mechanism in which each catecholamine cation is taken up in exchange for more than one H+. Measurements indicate that the stoichiometry is close to 2 H+/epinephrine cation, so the equilibrium epinephrine gradient is theoretically [E]in/[E]out = ([H+]in/[H+]out)2eFdelta psi/(RT). In deenergized ghosts, the epinephrine concentration gradient equals the [H+] gradient. This is consistent with a situation in which the H+ concentration gradient is in equilibrium with the membrane potential as described by the Nernst equation. Then, in the equation above, the membrane potential term (eFdelta psi/(RT)) will exactly cancel one power of the [H+] gradient, leaving [E]in/[E]out equal to [H+]in/[H+]out.