Bone is mechanically and structurally anisotropic with oriented collagen fibrils and nanometer-sized mineral particles aggregating into lamellar or woven bone. Direct measurements of anisotropic mechanical properties of sublamellar tissue constituents are complicated by the existence of an intrinsic hierarchical architecture. Methods such as nanoindentation provide insight into effective modulus values; however, bulk material properties cannot sufficiently be characterized since such measurements represent properties of near-surface volumes and are partially averaged over fibril orientations.[2–5] In this study, we focus on the material properties of bone at one single level of hierarchy. By measuring properties of individual parallel-fibered units of fibrollamellar bone under tension under controlled humidity conditions, an unusually high anisotropy is found. Here, we clearly demonstrate ratios as large as 1:20 in elastic modulus and 1:15 in tensile strength between orientations perpendicular and parallel to the main collagen fiber orientation in native wet bone; these ratios reduce to 1:8 and 1:7, respectively, under dry conditions. This extreme anisotropy appears to be caused by the existence of periodic, weak interfaces at the mesoscopic length scale. These interfaces are thought to be relevant to the proper mechanical and physiological performance of bone.