Spectrin and actin (S+A) are important extrinsic membrane proteins that are present as a layer on the inner face of the erythrocyte membrane. Using the polarographic technique, we have studied the ion permeability of adsorbed S+A monolayers at the mercury/water interface. The relative permeability of the S+A layer to cations and anions at different pH's is consistent with an isoelectric point (IEP) at a pH between 5 and 6. Below the IEP, the layer tends to impede the flow of cations. Above the IEP, the S+A layer impedes anions. Extrapolating to pH 7.4, it appears that the S+A layer is relatively impermeable to anions in the range where the erythrocyte membrane as a whole is very permeable to anions. The permeabilities of complete S+A monolayers to the CU++ complexes are estimated to be on the order of 10-4 cm/sec. Our observations indicate the existence of an anion-depleted compartment at the inner surface of the membrane, and suggest that the specialized anion carriers in the membrane penetrate this layer. © 1979, The Electrochemical Society, Inc. All rights reserved.