The fatigue life, under a constant load of 5000 lb/in², was determined for 67 specimens of compact bone of a standardized size obtained from five above-knee amputations. The specimens were unembalmed and tested wet in a Sonntag flexure fatigue machine with an automatic counter and shut-off. The average fatigue life to failure was 1,982,650 repetitions for 47 tibial specimens; 1,188,453 repetitions for 15 femoral specimens and 2,841,400 repetitions for 5 fibular specimens. The tibial specimens were analyzed according to thirds and quadrants. The average fatigue life of the middle third was 57% greater than that of the distal third and 206% greater than that of the proximal third. The average fatigue life of the posterior quadrant was 7% greater than that of the lateral quadrant, 23% greater than that of the medial quadrant and 50% greater than that of the anterior quadrant. Immobilization greatly reduces the fatigue life of bone, the average for specimens from a tibia of a paraplegic man being 194% less than that for specimens from other tibias. When the specimens from the paraplegic man were excluded the average fatigue life of the remaining 36 tibial specimens rose to 2,378,211 repetitions to failure.