Objectives for this research were to experimentally determine crack growth rates, da/dN, as a function of alternating stress intensity factor, ΔK, for specimens from lateral and dorsal regions of equine third metacarpal cortical bone tissue, and to determine if the results were described by the Paris law. In one set of experiments, specimens were oriented for crack propagation in the circumferential direction with the crack plane transverse to the long axis of the bone. In the second set of experiments, specimens were oriented for radial crack growth with the crack plane parallel to the long axis of the bone. Results of fatigue tests from the latter specimens were used to evaluate the hypothesis that crack growth rates differ regionally. The final experiments were designed to determine if crack resistance was dependent on region, proportion of hooped osteons (those with circumferentially oriented collagen fibers in the outer lamellae) or number of osteons penetrated by the crack, and to address the hypothesis that hooped osteons resist invasion by cracks better than other osteonal types. The transverse crack growth data for dorsal specimens were described by the Paris law with an exponent of 10.4 and suggested a threshold stress intensity factor, ΔKth, of 2.0 MPa-m1/2 and fracture toughness of 4.38 MPa-m1/2. Similar results were not obtained for lateral specimens because the crack always deviated from the intended path and ran parallel to the loading direction. Crack growth for the dorsal and lateral specimens in the radial orientation was described by the Paris law with exponents of 8.7 and 10.2, respectively, and there were no regional differences in the apparent ΔKth (0.5 MPa-m1/2) or fracture toughness (1.2 MPa-m1/2). Crack resistance was not associated with cortical region, proportion of hooped osteons or the number of osteons penetrated by the crack. The extent to which cracks penetrate osteons was influenced by whether the collagen fiber orientation in the outer osteon layers was circumferential or longitudinal. The majority of hooped osteons were skirted by the crack. The angle of interaction between the osteon and the crack was also significant in determining whether an osteon was penetrated.