Uniaxial fatigue tests were conducted of devitalized cortical bone specimens machined from human femora. Specimens were tested at strain ranges from 0.005 to 0.010 under physiologic loading rates. The influence of compressive, zero, and tensile mean strains on fatigue life and on the stress/strain histories during fatigue were examined. Results showed that bone fatigue is a gradual damage process accompanied by a progressive increase in hysteresis and a loss of bone stiffness. The total number of cycles to fatigue failure was influenced only by the total strain range and was not affected by mean strain. Bone was shown to have extremely poor fatigue resistance. Fully reversed cyclic loading to one half of the yield strain caused fatigue fracture in 1000 cycles. Biological implications. The bone regions which experience the highest strain ranges in vivo generally have a compressive mean strain. The results of this study indicate that mechanical fatigue damage accumulates more rapidly in these "compressive" areas than in "tensile" areas of bone.