1. Evidence for the existence in skeletal muscle of a specific cation binding system capable of lowering the chloride permeability was obtained by testing the effect of several metal ion species upon the efflux of (36)Cl from frog muscles equilibrated in high-KCl solution.2. Cu(2+), Zn(2+) and UO(2) (2+) ions, when present in concentrations of approximately 10(-4)M in inactive wash solution at pH 7.4 slowed the efflux of (36)Cl to half its original value. At pH 5.0, when the chloride permeability was already low as a consequence of hydrogen ion binding, these metal ions had little further effect.3. Presence of Ni(2+), Co(2+), Pb(2+), Ce(3+) and La(3+) in 10(-4)M or higher concentrations had no detectable influence on the (36)Cl efflux. Wide variations in Ca(2+) concentration were similarly ineffective.4. The influence of more adsorbable anions on the chloride permeability was examined at different pH values. Extracellular iodide greatly slowed the rapid efflux of (36)Cl into alkaline solution. In acid solutions, when the chloride permeability was already low, the effect of iodide was less pronounced, but still demonstrable. The chloride permeability was consequently increased to a lesser extent by a rise in pH in the presence of iodide.5. The efflux of iodide and bromide was measured at different pH values under conditions of self exchange. In alkaline solution the permeabilities to iodide and bromide were considerably lower than that to chloride. In acid solution the membrane differentiated less between anion species of different adsorbability.