The effect of ATP depletion on the protection of rabbit eryth- rocytes by amphiphilic substances in posthypertonic shock conditions was studied. For this, the level of hemolysis in posthypertonic shock of native and ATP-depleted erythrocytes in the presence of amphiphilic substances was determined. It was shown that ATP depletion reduces posthypertonic cell damage by 15-17% both at 0°С and at 37°С. It was found that amphiphilic compounds are able to protect rabbit erythrocytes in conditions of posthypertonic shock, but only at a temperature of 0°С. In conditions of ATP-depletion of cells, only anionic sodium decyl sulfate and nonionic decyl-β,D-glucopyranoside retain their protective effect in posthypertonic shock condi- tions, whereas cationic chlorpromazine and trifluoroperazine lose this ability. This can be explained based on the features of the incorporation of amphiphiles into the erythrocyte membrane. All studied amphiphilic compounds increase the level of damage in both control and ATP-depleted cells under conditions of posthypertonic shock at a temperature of 37°C. Probably, easier intercalation and increased fluidity of the membrane at this temperature destabilize the bilayer and reduce the protective effect of amphiphilic compounds.