Material properties and their variations in individual bone organs are important for understanding bone adaptation and quality at a tissue level, and are essential for accurate mechanical models. Yet material property variations have received little systematic study. Like all other material property studies in individual bone organs, studies of the human mandible are limited by a low number of both specimens and sampled regions. The aims of this study were to determine: 1) regional variability in mandibular material properties, 2) the effect of this variability on the modeling of mandibular function, and 3) the relationship of this variability to mandibular structure and function. We removed 31 samples on both facial and lingual cortices of 10 fresh adult dentate mandibles, measured cortical thickness and density, determined the directions of maximum stiffness with a pulse transmission ultrasonic technique, and calculated elastic properties from measured ultrasonic velocities. Results showed that each of these elastic properties in the dentate human mandible demonstrates unique regional variation. The direction of maximum stiffness was near parallel to the occlusal plane within the corpus. On the facial ramus, the direction of maximum stiffness was more vertically oriented. Several sites in the mandible did not show a consistent direction of maximum stiffness among specimens, although all specimens exhibited significant orthotropy. Mandibular cortical thickness varied significantly (P < 0.001) between sites, and decreased from 3.7 mm (SD = 0.9) anteriorly to 1.4 mm posteriorly (SD = 0.1). The cortical plate was also significantly thicker (P < 0.003) on the facial side than on the lingual side. Bone was 50–100% stiffer in the longitudinal direction (E3, 20–30 GPa) than in the circumferential or tangential directions (E2 or E1; P < 0.001). The results suggest that material properties and directional variations have an important impact on mandibular mechanics. The accuracy of stresses calculated from strains and average material properties varies regionally, depending on variations in the direction of maximum stiffness and anisotropy. Stresses in some parts of the mandible can be more accurately calculated than in other regions. Limited evidence suggests that the orientations and anisotropies of cortical elastic properties correspond with features of cortical bone microstructure, although the relationship with functional stresses and strains is not clear. Am J Phys Anthropol 120:252–277, 2003. © 2003 Wiley-Liss, Inc.