Mechanical strains produced by functional loading influence the cellular activities responsible for normal appendicular bone development and maintenance. Contemporary investigations recognize that modeling and remodeling processes mediate the strain-related structural and material adaptations produced during normal bone development. However, the goals towards which such adaptations are directed remain unclear. hypothesized that a possible objective for regional variations in material organization between cortical locations of a limb bone diaphysis may be the maintenance of uniform stresses throughout a bone's crosssection. Examining mature ovine radii at mid-diaphysis, they found that the narrower caudal 'compression' cortex had a lower elastic modulus than the thicker, less-highly strained cranial (dorsal) 'tension' cortex. Riggs et al. (1993) reported similar elastic modulus differences between the cranial 'tension' and caudal 'compression' cortices of the equine radius at mid-diaphysis, even though these regions have nearly equivalent cortical thickness. These elastic modulus differences were attributed to significant regional variations between the cranial and caudal cortices, including more oblique-to-transverse collagen fiber orientation, lower mineral content, and increased remodeling with secondary osteons in the caudal cortex. These authors suggested that since cranial versus caudal stresses are significantly different in each species, and the associated remodeling responses appeared to amplify this difference, the non-uniform stress distribution represents a goal of developmental adaptation. Because yield and ultimate stress of cortical bone are lower in tension than in compression (Reilly and Burstein, 1975), and the nonuniform stress distributions of ovine and equine radii resulted in roughly equivalent safety factors between the cranial and caudal cortices, the achievement of equivalent or uniform 'regional' safety factors (e.g. cranial cortex = caudal cortex) was offered as an explanation for a major goal of adaptation in these bones Riggs et al., 1993).Safety factors, when considered in skeletal biomechanics, usually refer to an entire bone (Rubin and Lanyon, 1982;Biewener, 1993). In the present study we further examine the idea of 'regional' safety factors; for example, those from a distinct cortical location within the same transverse crosssection Riggs et al., 1993). In either case, It has been hypothesized that a major objective of morphological adaptation in limb-bone diaphyses is the achievement of uniform regional safety factors between discrete cortical locations (e.g. between cranial and caudal cortices at mid-diaphysis). This hypothesis has been tested, and appears to be supported in the diaphyses of ovine and equine radii. The present study more rigorously examined this question using the equine third metacarpal (MC3), which has had functionally generated intracortical strains estimated by a sophisticated finite element model. Mechanical properties of multiple mid-diaphyseal specimens ...