Summary Basic research in canine mechanics must be performed to better understand the forces and moments the appendicular skeleton must withstand. This type of research may allow surgeons to make substantial advances in total joint replacement and fracture fixation design and may enhance our understanding of bone remodeling and fracture occurrence in relation to exercise and trauma. In our study, craniocaudal bending stiffness, mediolateral bending stiffness, axial compressive stiffness, and torsional stiffness of the humerus, femur, radius, and tibia of dogs was determined, using nondestructive bending, compression, and torsional tests. Entire diaphyseal and middiaphyseal properties of these long bones were evaluated. Bones also were tested to failure in torsion to quantify the failure properties of these long bones. Left to right variability was examined to validate the use of contralateral limbs as the control condition for experimental studies. There were no significant right to left differences in entire diaphyseal mechanical properties for any of the long bones, except for compressive stiffness of femurs. Homotypic differences in entire diaphyseal mechanical properties, if present, ranged from 8.0 to 35% for the 4 long bones (power = 0.8). For middiaphyseal mechanical properties, there were no significant right to left differences in the 4 long bones, except for craniocaudal bending stiffness of tibias. The homotypic differences in middiaphyseal mechanical properties, if present, ranged from 7.2 to 62% for the 4 long bones (power = 0.8). In all bones and loading modes, middiaphyseal stiffness was greater than entire diaphyseal stiffness (P < 0.0001). In torsional energy to failure and maximal torsional displacement at failure, entire diaphyseal properties were significantly (P < 0.0001) higher than middiaphyseal properties. In axial compression, there were no entire diaphyseal or middiaphyseal mechanical property differences among the 4 bones. In craniocaudal bending, humeruses were significantly (P < 0.05) more stiff than the other 3 bones in the entire diaphysis, and were more stiff than radiuses and tibias in the middiaphysis. In mediolateral and craniolateral bending and in torsion, radiuses were less stiff, in the entire diaphysis and in the middiaphysis, than were the other 3 bones (P < 0.05). In torsion, there were no significant differences in energy to failure or in maximal displacement at failure among the 4 bones, either in the entire diaphysis or middiaphysis.