The objective of the present study was to substantiate the rationale for the choice of optimal pressure under which a solution should be administered into the tissues overlaying mandibular periosteum for the purpose of local infiltration anesthesia. Material and methods. The anesthetic (a 4% articaine solution containing epinephrine at a concentration of 1:100,000) was administered under the constant pressure in the range from 228 to 1140 mm Hg. The effectiveness of anesthesia was estimated from the threshold pain sensitivity of teeth taking into consideration the time and the duration of the maximum anesthetic effect. Results. It was demonstrated that increasing pressure accelerates the development and prolongs the duration of the maximum anesthetic effect. These variables no longer change significantly after a certain pressure level is achieved. The analysis of the data obtained made it possible to determine the minimal and maximal times of development and duration of the pain-relieving effect after each consecutive rise in the pressure of administration of the anesthetic solution. It is concluded that these parameters can be used as the reference values in the practical work. The optimal pressure is considered to be 608 mm Hg since it ensures the rapid increase of anesthetic effect and its longest persistence at the maximum level. Moreover, administration of the anesthetic solution under such pressure allows to most reliably predict characteristics of the pain-relieving effect and reduces to a minimum the difference between its most and least pronounced manifestations. A further rise in the pressure does not lead to a significant improvement of the anesthetic effect. All its characteristics become much worse at a lower administration pressure.