Content Summary : Although fatigue damage in bone induced by cyclic loading has been recognized as a problem of clinical significance, few fracture mechanics based studies have investigated how incipient cracks grow by fatigue in this material. In the present study, in vitro cyclic fatigue experiments were performed in order to quantify fatigue-crack growth behavior in human cortical bone. Crack-growth rates spanning five orders of magnitude were obtained for the extension of macroscopic cracks in the proximal-distal direction; growth- rate data could be well characterized by the linear-elastic stress-intensity range, using a simple (Paris) power law with exponents ranging from 4.4 to 9.5. Mechanistically, to discern whether such behavior results from ‘‘true’’ cyclic fatigue damage or is simply associated with a succession of quasi-static fracture events, cyclic crack-growth rates were compared to those measured under sustained (non-cyclic) loading. Measured fatigue-crack growth rates were found to exceed those ‘‘predicted’’ from the sustained load data at low growth rates ( B3 10 10 to 5 10 7 m/cycle), suggesting that a ‘‘true’’ cyclic fatigue mechanism, such as alternating blunting and re-sharpening of the crack tip, is active in bone. Conversely, at higher growth rates ( B5 10 7 to 3 10 5 m/cycle), the crack-growth data under sustained loads integrated over the loading cycle reasonably predicts the cyclic fatigue data, indicating that quasi-static fracture mechanisms predominate. The results are discussed in light of the occurrence of fatigue-related stress fractures in cortical bone.