CLASSICALLY, there is a direct correlation between the lipophilic nature of a molecule and its rate of permeation across a biological membrane,^1,2 so cell membranes should be more permeable to small, neutral molecules than they are to charged molecular species of similar size. Consequently, the distribution of NH₄⁺ in biological systems is generally believed to be due to the rapid diffusion and equilibration of lipophilic NH₃ across cell membranes and the accumulation of NH₄⁺ to be governed by pH differences between compartments. Here we report that renal tubule cells from the medullary thick ascending limb of Henle have an apical membrane which is not only virtually impermeable to NH₃, but is also highly permeable to NH₄⁺. These remarkable properties have been incorporated into a model which explains how this renal epithelium can mediate vectorial movement of NH₄⁺ between compartments of equal pH^3,4.