—The biophysical properties of lymphocytes under mechanical deformations of blood cells were investigated. An in vitro model of mechanical “stress” helps to activate components of the purinergic signaling system of blood cells through ATP-dependent receptors. It was established that under mechanical stress, the level of ATP in the blood increased by 2.3 times compared to the control, the cell surface charge of lymphocytes decreased, rigidity increased, and the strength of adhesion between lymphocytes and erythrocytes became stronger. Our findings indicate that the ATP molecules are involved in the regulation of biophysical properties of the plasmalemma of lymphocytes that, in turn, may lead to a change in the receptor complexes on the surfaces of immunocompetent cells.