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Existing literature shows that the rates of stress fracture for female athletes and female army recruits are higher than their male counterparts. In this study, we used an ex vivo rat model to investigate the fatigue response of female and male bones. We determined the strain versus number of cycles to failure (<jats:italic>S<\/jats:italic>\/<jats:italic>N<\/jats:italic>) for each sex and found that for a certain initial strain (5,000\u20137,000 \u00b5\u03b5) female bones have shorter fatigue life. To further characterize the bone response to fatigue, we also determined the creep that occurred during the fatigue test. From the creep data, for a certain strain range, female bones accumulated greater residual strains and reached the critical strain at a faster rate. In summary, this study demonstrates that female rat bones have a lower resistance to fatigue in the absence of a physiological response such as muscle fatigue or osteogenic adaptation. From these results, we hypothesized that creep was the underlying mechanism that accounted for the fast deterioration of female bones during fatigue. \u00a9 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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