The influence of torsional loading on the fatigue life of cortical bone was investigated by conducting in vitro testing. Fatigue tests were conducted on cylindrical dumbbell bovine cortical bone specimens in an environmental chamber under axial loading, torsional loading and various combinations of axial-torsional loading where the phase relationship and relative magnitudes of axial and torsional loadings were systematically varied. It was found that the superposition of torque on axial loading reduced the fatigue life of cortical bone. The reduction in fatigue life was significant when the maximum shear stress was greater than 59% of the maximum normal stress. The magnitude of reduction in the fatigue life of bone at low as well as high levels of axial loading depended on the magnitude of torsional loading, but was independent of the phase angle by which the torsional loading lagged the axial loading. Furthermore, oblique fracture profiles, characteristic of torsion-induced failure, were observed for combined axial-torsional load cases. Based on these results, it is suggested that torsional loading plays a significant role in determining the fatigue life of cortical bone. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.