The tenosynovium in the human carpal tunnel is connected to the flexor tendons and the median nerve by the subsynovial connective tissue (SSCT). The most common histological finding in carpal tunnel syndrome (CTS), a compression neuropathy of the median nerve, is noninflammatory fibrosis of the SSCT. The relationship, if any, between the fibrosis and nerve pathology is unknown, although some have speculated that a change in the SSCT volume or stiffness might be the source of the compression. Yet, while animal models have been used to study the physiology of nerve compression, so far none have been used to study the relationship of the SSCT pathology to the neurophysiological abnormalities. The purpose of this study was to identify animal models that might be appropriate to study the interaction of SSCT and nerve function in the development of CTS. The front paws of a rat, rabbit, dog, and baboon were dissected. The carpal tunnel anatomy and SSCT of these animals were also examined by light and scanning microscopy and compared to the relevant human anatomy and ultrastructure. The carpal tunnel anatomy and contents of the baboon and rabbit are similar to humans. The canine carpal tunnel lacks the superficial flexor tendons and the rat carpal tunnel is very small. The human, baboon, and rabbit specimens had very similar organization of the SSCT, and content of the carpal canal. We conclude that, while both the baboon and rabbit would be good animal models to study the relationship of the SSCT to CTS, the rabbit is likely to be more practical, in terms of cost and animal care concerns.