The effects of trifluoroperazine and sodium decyl sulfate on posthypertonic shock of human and rabbit erythrocytes were studied. For this purpose, the level of hemolysis in posthypertonic shock and the percentage of potassium ions released from erythrocytes in dehydration and rehydration solutions in the presence of trifluoroperazine and sodium decyl sulfate were determined. It is shown that the protective effect of amphiphilic compounds is manifested at 0°C, but not at 37°C. There is a decrease in the level of hemolysis in a certain concentration range of each of the studied substances. It was found that human erythrocytes are more sensitive to the protective action of the studied amphiphilic compounds and are characterized by a wider range of protective concentrations. This could be explained by the different lipid composition of the erythrocyte membranes of the studied mammals. Measurement of the leak of potassium ions in dehydration and rehydration media in the presence of amphiphilic compounds suggested that the latter do not affect the permeability of the membrane of mammalian erythrocytes for potassium in posthypertonic shock. Based on the obtained results and literature data, it is assumed that the protective effects of trifluoroperazine and sodium decyl sulfate occur independenly of the formation of temporary defects in permeability for potassium ions, but involve an increase in the cell surface area due to the incorporation of amphiphilic molecules. This results to an increase in the critical hemolytic volume of erythrocytes and reduction in the level of damage during change from hypertonic conditions to isotonic ones.