OBJECTIVES: Comparing study of acute toxicity of new synthesized piperidine derivative after a single dose and by the use of Computer Assisted Design. Nowadays the use of traditional methods of study of acute toxicity is severely limited, according to the humanization of experimental studies. In these conditions, Computer Assisted Design/CAD is more applicable, when computer recreates the structure of the chemical in a three-dimensional image. METHODS: in the Institute of Chemical Sciences synthesized new derivatives of piperidine under laboratory code МАВ118, МАВ121, МАВ124, МАВ129, МАВ130, МАВ131, МАВ134. Acute toxicity was studied by traditional methods: intraperitoneal, subcutaneous injection of 4% water solutions of local anesthetics to white mice of both sexes where used. Toxicity assessment was carried out on the base of LD50 rate. The calculation of quantum chemical parameters was carried out by semiempirical Hartree-Fock method with the assistance of a calculation program MOPAC 6. RESULTS: The results of the calculations of LD50 allow to select group of low toxicity (MAV 121, 129 MAV, MAV, 130, МАВ134) and moderate toxicity (MAV 118, MAV, 124, МАВ131) compounds. Analysis of the relation between the toxicity and quantum-chemical characteristics was performed using Computer Assisted Design. Low-toxic compounds were characterized by: high level of stability in the form of neutral molecules, due to the negative values of heat of formation and full of energy, combined with a relatively low reactivity, evidenced by the positive dipole moment. Compaund with moderate toxicity form a neutral molecule and H-cation, with H-cation significantly less stable than H-cation of low-toxicity compounds, as well as lower dipole moment. Compaund with moderate toxicity are less reactive than low toxicity ones. CONCLUSIONS:  The results indicate the possibility of applying the parameters of quantum chemistry and molecular mechanics to predict the toxicity of derivatives of piperidine and optimization of primary screening