AbstractParachloromercuribenzenesulfonate (PCMBS) has two opposing effects on the influx of Rb+ into red blood cells. The ouabain‐insensitive component, indicative of passive permeability of the membrane to cations, is increased whereas the ouabain‐sensitive or active transport component is inhibited. The increased passive permeability is paralleled by the action of PCMBS on net K+ efflux into a K+‐free medium. Inhibibition of active transport of Rb+ is paralleled by the inhibitory action of PCMBS on net Na+ efilux from Na+‐rich cells. Both effects are reversed rapidly by the penetrating sulfhydryl compound, cysteine, and considerably more slowly by the non‐penetrating sulfhydryl compound, ovalbumin. Measurements of PCMBS binding and of elution in the presence of cysteine and albumin indicate that only a fraction of the total sulfhydryl groups of the membrane is involved in either the effect on permeability or transport, and that the affected groups are located within the interior of the membrane.