Accurate determination of intrinsic permeability coefficients is critical to the development of structure-permeability relationships and liposomal delivery systems. The apparent release rate of a drug from liposomes may reflect not only its intrinsic permeability coefficient and barrier properties but also a variety of underlying equilibria including drug ionization, membrane binding or complexation, and kinetic processes such as buffer exchange. Additionally, transport of ionizable drugs that are initially at high concentrations in liposomes can generate or dissipate pH gradients across the barrier causing deviations from classical pH-permeability profiles. In this study, the liposomal release of a model amine (tyramine) is determined as a function of drug loading, intravesicular pH, and buffer composition. Kinetic models are derived to study effects of such equilibria (e.g., ionization, membrane binding) and kinetic processes (e.g., pH drift and acid/base carriers). All equilibrium constants needed for the models were independently measured and used. The barrier properties of the lipid bilayers under the experimental conditions were assessed by monitoring the transport of mannitol and bretylium as a function of pH. A corrected intrinsic permeability coefficient of 0.04 cm/s was in close agreement with the value predicted from the barrier domain model for bilayer permeability, suggesting that all perturbing factors were properly addressed.