Background Functionally induced strains provide epigenetic signaling for bone modeling and remodeling activities. Strain gauge documentation of the equine third metacarpal reveals a neutral axis passing through the craniolateral cortex, resulting in a narrow band of cortex loaded predominantly in tension, with the remainder of the cortex experiencing a wide range of compression strain magnitudes that are maximal in the caudomedial cortex. This predictable strain pattern provides a model for examining the hypothesis that strain mode, magnitude, and strain energy density are potential correlates of compact bone structural and material organization. Methods Structural and material variables were quantified in nine equine (standard breeds) third metacarpals for comparison with the in vivo strain milieu that was evaluated in thoroughbred horses. The variables quantified included secondary osteon population density (OPD), fractional area of secondary bone (FASB), fractional area of porous spaces, collagen fiber orientation, mineral content (% ash), and cortical thickness. Each bone was sectioned transversely at 50% of length, with subsequent quantification of eight radial sectors and three intracortical regions (periosteal, middle, endosteal). Linear regression analysis compared these variables to magnitudes of corresponding regional in vivo longitudinal strain, shear strain, and strain energy density values reported in the literature. Results The craniolateral (“tension”) cortex of this bone is distinguished by its 30% lower FASB and with the lateral cortex exhibits 20% darker gray level (more longitudinal collagen) compared with the average of all other locations. Conversely, the remaining (“compression”) cortices as a group have a high OPD, are more extensively remodeled, and contain more oblique-to-transverse collagen. The caudal cortices (caudomedial, caudal, caudolateral) are significantly thinner (P < 0.01) and have 4% lower mineral content (P < 0.05) than all other locations. Moderately strong correlations exist between collagen fiber orientation and normal strain (r = 0.752) and shear strain (r = 0.555). When normal and shear strains were transformed to their respective absolute values, thus eliminating the effects of strain mode (tension vs. compression), these correlation coefficients decreased markedly. Conclusions Collagen fiber orientation is related to strain mode and may function to accentuate rather than attenuate bending. These differences may represent adaptations that function synergistically with bone geometry to promote a beneficial strain distribution and loading predictability during functional loading. © 1996 Wiley-Liss, Inc.