A dose-response relationship has been shown between loading frequency and cortical bone adaptation for frequencies of up to 10 Hz, and is presumed to persist with further increases in frequency. Studies herein aimed to investigate cortical bone adaptation to loading frequencies of 1, 5, 10, 20 and 30 Hz. Two studies were performed in adult C57BL/6 mice using the ulna axial compression-loading model. In the first study, the histomorphometric response of the ulna was studied when loaded for 120 cycles day−1 for 3 days at one of the five frequencies and one of two load magnitudes (1.5 or 2.0 N). In the second study, the changes in ulna geometry and mechanical properties were studied following loading for 5 min day−1, 3 days week−1 for 4 weeks at one of the five frequencies and one of two load magnitudes (1.0 or 1.6 N). Preliminary strain gauge measurements showed that frequency had no effect on mechanical strain per unit load. In study 1, loading frequency significantly influenced bone adaptation when loading at 2.0 N, with loading at 10 Hz resulting in significantly greater adaptation than with loading at other frequencies. In study 2, loading frequency significantly influenced the change in geometry when loading at 1.6 N, with loading at 5, 10 or 30 Hz resulting in significantly greater change than with loading at 1 Hz. Loading at 5 Hz also resulted in significantly greater change than with loading at 20 Hz. No frequency effect was found on any of the mechanical properties at either load. Overall, we found cortical bone adaptation to mechanical loading to increase with increasing loading frequency up to 5–10 Hz and to plateau with frequencies beyond 10 Hz. The mechanism for this nonlinear frequency response is not known;​ however, based on strain gauge measurements, we do not believe it resulted from dampening associated with high frequency loading through the flexed carpal joint. The obtained findings may relate to the mechanism of mechanotransduction within the bone. This requires further investigation.