Compact bone specimens were cyclically loaded in uniaxial tension for one million cycles; loading was performed at either of two physiological strain rates (0.01 s-1 or 0.03 s-1) and a physiological strain range (0-1200 microstrain). Microdamage in loaded and nonloaded control specimens was then assessed histomorphometrically. Fatigue, evidence by stiffness loss, was observed at both strain rates and was significantly greater in specimens loaded at the high experimental strain rate than in specimens loaded at the low strain rate. Morphologically, this fatigue corresponded to increased numbers of microcracks in the bone. These data show that fatigue and resultant microdamage are realistic expectations of cyclic loading within the physiological strain range. The rate at which strains are developed influences the fatigue behavior of compact bone, suggesting that cyclic loading at high physiological strain rates, characteristic of vigorous activities, is more damaging to compact bone than loading at lower physiological strain rates.