Manipulation and mobilization are two forms of manual therapy commonly employed in the management of musculoskeletal disorders. Spinal manipulation and mobilization are often distinguished from one another by reference to certain biomechanical parameters such as peak force, duration and magnitude of translation. However, as of yet, there is relatively little research which distinguishes between them in terms of neurological mechanisms or clinical effectiveness. Theories concerning the mechanisms underlying the therapeutic effects of manipulation and mobilization commonly make reference to mechanical events such as the release of entrapped tissue or the disruption of intra-articular adhesions. Relatively less attention is given to neural effects. In this paper, we hypothesize that, at least in part, spinal manipulation preferentially influences a sensory bed which, in terms of anatomical location and function, is different from the sensory bed influenced by spinal mobilization techniques. More specifically, we hypothesize that manipulation may particularly stimulate receptors within deep intervertebral muscles, while mobilization techniques most likely affect more superficial axial muscles. In part, our rationale for this hypothesis is based on differences in mechanical advantage of the respective manual procedures on multi-segmental versus short intervertebral muscles.