The anion and cation permeability of the red blood cells can be modified by a large variety of chemical agents. The interaction of many of these agents with the membrane seem to involve a reaction with positively charged groups. A series of unrelated amphiphilic compounds which should not react with amino-groups nevertheless, produce reciprocal effects on anion and cation permeability. An important exception to the pattern of reciprocal anion-cation effects is found with the disulfonic stilbene derivate, SITS, developped by Maddy as a covalent bonding agent for amino groups of the cell surface. As derivative we used H2DIDS. This agent is just effective as other in reducing anion permeability, but has no effect on cation permeability. The unique specificity of H2DIDS has been attributed to its inability to penetrate into membrane and reacts with a small sites superficially located on the outer face of the membrane. We studied the inhibition of 35SCN efflux by mean H2DIDS in the human red cell ghosts as a function of concentration, incubation time, pH in the medium. We found that the best concentration to obtain the maximum of inhibition is about 50 microM H2DIDS, increasing H2DIDS concentration does not produce further inhibition. Incubation time must be around one hour, increasing the incubation time, there isn't any variation in the inhibition. H2DIDS acts better in a basic range then in an acid one.