The transmembrane potential of frog sartorius fibers in normal Ringer's solution is increased by a few millivolts following a fall in pH of the external medium. The same result is observed in either a bicarbonate–CO2 or a phosphate buffer system. The hyperpolarizing response is still observed when sodium in the Ringer solution is replaced by choline. Immediately after increasing the external potassium from 2.5 to 10 meq/l this effect is reversed. On changing the external potassium back to 2.5 meq/l the effect returns and is considerably enhanced. Chloride loading by presoaking muscles in isotonic KCl and transferring to sucrose causes a reversal of membrane potential and leads to an exaggerated pH effect. These observations, together with the fact that transmembrane conductance falls at a lower pH, suggest that hydrogen ions act mainly by lowering PCl. When ECl > Em, hydrogen ions will increase transmembrane potential. This effect may form the basis of a local control mechanism by which cell activity and local metabolic conditions regulate transmembrane potential.