This communication presents a physicochemically-based analysis of direct interactions between the basic components of e-liquids (i.e., glycerol (GL) and propylene glycol (PG) that form the aerosol in electronic nicotine delivery systems (ENDS)) and the model pulmonary surfactant: MPS (Survanta). Experimental studies were done using dynamic drop tensiometer (PAT-1M, Sinterface, Germany) in simulated conditions of the respiration, i.e., during periodic breathing-like variations of the MPS air/ liquid interface at the physiological temperature. Influence of GL, PG and GL/PG mixtures (20-80%) on the interfacial dynamics of the MPS system was studied at a wide concentration range of these ingredients simulating different doses of inhaled e-cigarette aerosols deposited in the pulmonary region. Estimates of the average e-liquid concentration were calculated based on a deposition model for orally inhaled aerosols. MPS dynamics was assessed on the basis of surface rheological parameters, which quantitatively describe the response of the active air/liquid (pulmonary) interface to the mechanical deformations (expansion and contraction) during breathing. The results show that GL, PG and their mixtures induce evident alterations of the original MPS properties (e.g., a decrease in the surface tension amplitude, surface elasticity and surface viscosity) only at very high concentration levels, which exceed by more than 100-fold the average concentration expected after a typical vaping session. It is also demonstrated that the overall effect of PG is stronger than that of GL. The influence of e-liquid constituents on the pulmonary surfactant is discussed on the basis of their adsorption and desorption at the air/liquid region during oscillatory variations of the interfacial area. Discussed physicochemical phenomena may be related to certain changes in the pulmonary surfactant function in vivo. Therefore, the findings from the presented studies should be included into the safety assessment of inhaled ENDS-vapor, also in case of nicotine-free products.