Urea transport across amphibian membranes is influenced by interactions with the membrane, the solvent and other solutes. One case of solute interaction, that in which the two species are chemically identical, is investigated here. Because of the effects of hypertonic urea on permeability, the demonstration of interaction required consideration of the ratior of bidirectional tracer permeabilities. Mucosal-to-serosal (M→S) and serosal-to-mucosal (M←S) tracer urea fluxes were determined in paired toad urinary bladders, in the absence and presence of abundant urea. In the control state,r was 1.0. Addition of 0.3m urea toM increasedr, and toS decreasedr. These results indicate coupling of abundant and tracer urea flows (isotope interaction), probably occurring in specialized regions. The effects persisted after the addition of antidiuretic hormone, despite the opposing influence of osmotic water flow. Quantitatively different effects of mucosal and serosal hypertonicity, both with and without antidiuretic hormone, are explicable in terms of heterogeneous parallel and series permeability barriers.