Possible transport mechanisms of chloride across the mammalian proximal tubule include both active and passive components and, accordingly, transcellular and intercellular transport routes. Experiments are described in which the possibility of electroneutral anion exchange across the apical cell membrane of proximal tubule cells is evaluated. Experiments in brushborder vesicles of the rabbit kidney cortex have shown the existence of a chloride/formate exchange process. In addition, evidence is presented that formic acid is crossing the brushborder membrane of rabbit renal cortex by non-ionic diffusion. A transport schema is developed in which formate/chloride exchange and sodium/hydrogen exchange in parallel with recycling of formic acid by non-ionic diffusion can account for the electroneutral transport of sodium chloride. Perfusion studies in isolated rabbit straight and convoluted tubules show significant transport stimulation by submillimolar concentrations of formate. Thus, chloride/formate exchange is a possible mechanism for active, transcellular chloride movement across the mammalian proximal tubule.