Objectives: The purpose was to measure the interstitial fluid pressure generated from tissue resistance during administration of local anesthetic solution at 4 anatomic locations within the oral cavity and to determine whether differences in soft tissue density affect interstitial fluid pressure when anesthetic solution is administered at a fixed flow rate. Method and Materials: A computer-controlled local anesthetic delivery device (CompuFlo, Milestone Scientific) that records and stores pressure data during a subcutaneous injection was used. Subjects consisted of adult patients seeking routine dental care that required local anesthesia. A total of 200 injections were administered and fluid pressure readings recorded. Injections were divided into 4 groups of 50: group 1-intraligamentary injections (PDL); group 2-palatal injection, anterior middle superior alveolar nerve block; group 3-supraperiosteal buccal infiltrations, and group 4-inferior alveolar nerve blocks. For all injections 1 cartridge (1.8 mL) of lidocaine containing 1:100,000 concentration of epinephrine was administered at a fixed flow rate of 0.005 mL/sec. Results: One-way analysis of variance (ANOVA) revealed that the data were statistically significant (P .001), with corresponding mean values as follows: group 1, 293.98 psi; group 2, 68.16 psi; group 3, 11.50 psi, and group 4, 9.76 psi (F-ratio of 2371.933). Groups 1 and 2 were different from all other groups; groups 3 and 4 were not statistically different from each other. Conclusion: Interstitial resistance to fluid pressure can be measured during administration of 4 different local anesthetic injections used in dentistry. Based on fluid pressure and tissue resistance characteristics, a soft tissue density classification was defined. Keywords: computer-controlled drug delivery system, computer-controlled local anesthetic delivery system, dental, injection pressure, local anesthesia, local anesthetic technique, tissue pressure