Repetitive physiologic loading is widely believed to be beneficial in maintaining skeletal integrity. However, repetitive loading is also associated with bone injuries, including stress fractures and osteoporotic fractures, indicating that under certain conditions repetitive physiologic loading decreases the functional capacity of bone. Our objective was to identify the response of bone to excessive repetitive loading in adult rats. Male and female rats (8-9 months old) were exposed to 2 hours of treadmill running each day for 10 or 30 consecutive days. We examined bone response using biochemical, densitometric, and monotonic, relaxation, and cyclic mechanical outcomes. Urinary deoxypyridinoline, a marker of bone resorption, was not significantly affected by running nor were tibial or femoral bone mineral density (BMD) (P > 0.05). Tibial mechanical properties following running were not decreased (P > 0.05). We did observe a slight decrease in displacement to failure (P < 0.05) and energy to failure (P = 0.10) of the proximal femur. These findings indicate that 14,000 physiologic loading cycles per day did not increase systemic bone resorption levels or substantially degrade the mechanical properties of long bone in adult rats. The lack of response to low magnitude, high cycle number physiologic loading is consistent with the view that a metabolic bone disturbance, in addition to repetitive loading, may be necessary for the development of the stress injury in the adult skeleton.