A great challenge in anesthesia for the present days consists in increasing local anesthetic (LA) effect but not its toxicity. Lidocaine (LDC) is a moderate-action local anesthetic commonly used in dentistry, mainly in association with vasoconstrictors, added in order to increase duration of anesthesia. Nevertheless, the use of vasoconstrictors is either not recommended or contraindicated, in many cases. The delivery of LA in liposomes has been investigated as another approach to reach prolonged anesthetic action, without increasing the systemic toxicity induced by it. We have previously reported (Brunetto, G.B. et al, XXXIII SBBq Annual Meeting, abstract H-67, 2004) the preparation of a liposomal formulation of lidocaine, which presented an enhanced analgesic effect, in comparison to LDC in water. Here we describe a novel liposomal formulation for lidocaine, prepared with hydrogenated soy phosphatidylcholine, cholesterol and mannitol (3:1:1.25 mole %); after spray-dryer processing the solid particles were hydrated with 20 mM HEPES buffer plus 150mM NaCl, pH 7.4. The nonciceptive effect of this soya-liposome lidocaine (SL-LDC) formulation was compared to that of lidocaine solutions (with and without vasoconstrictor), through the rat infraorbital-nerve blockade test. The analgesic effects of SL-LDC did not surpass those of the lidocaine plus epinephrine solution (p<0.001, Mann-Whitney test), what could be assigned to the intrinsic vasodilator activity of lidocaine, that counterbalanced the long-lasting release of the LA from the liposomes and favours its clearance, leaving less LDC molecules available for neural blockade. By the other hand, SL-LDC produced an increase in the anesthetic effect (66%) and in the time for recovery (55%) of infraorbital-nerve blockade, in comparison to LDC without epinephrine (p<0.001), that must be related to the longer residence-time of the liposomal formulation in the site of injection. These results suggest that SL-LDC could be used in dentistry’s analgesia procedures, when vasoconstrictor usage is either not recommended or contraindicated.          Supported by CAPES and CNPq.