Four new bis-macrocyclic bolaamphiphiles were prepared to explore the effects of hydrophobic substitutions on ion transport. In bilayer vesicles the new compounds were remarkably similar to more hydrophilic derivatives prepared previously. Planar bilayer conductance experiments showed the new compounds induced an unique current-time signal consisting of a rapid rise time, followed by a slower decay time. Signal shape was cation dependent and was related to a modest selectivity between cations. Cation-anion selectivity was very high, approaching an ideal cation selectivity. One compound also showed voltage dependence of the signal shape and duration. Qualitative changes in signal shape, duration, and voltage dependence were provoked by variation in the electrolyte pH and by masking the head-group electrostatic interactions with low levels of barium ions. A model for the signal shape is proposed, involving a rapid current rise due to aggregate restructuring, followed by slower decay due to development of the local Donnan potential that results from the high cation-anion selectivity.Key words: ion channel, synthesis, bilayer membrane, bilayer clamp, mechanism.