We present a novel theory to predict the contact angle of water on amphoteric surfaces, as a function of pH and ionic strength. To validate our theory, experiments were performed on two commonly used amphoteric materials, alumina (Al2O3) and titania (TiO2). We find good agreement at all pH values, and at different salt concentrations. With increasing salt concentration, the theory predicts the contact angle-pH curve to get steeper, while keeping the same contact angle at pH = PZC (point of zero charge), in agreement with data. Our model is based on the amphoteric 1-pK model and includes the electrostatic free energy of an aqueous system as well as the surface energy of a droplet in contact with the surface. In addition, we show how our theory suggests the possibility of a novel responsive membrane design, based on amphoteric groups. At pH ∼ PZC, this membrane resists flow of water but at slightly more acidic or basic conditions the wettability of the membrane pores may change sufficiently to allow passage of water and solutes. Moreover, these membranes could act as active sensors that only allow solutions of high ionic strength to flow through in wastewater treatment.