Spinal manipulation is a manual therapy approach commonly employed by chiropractors, osteopaths and manipulative physiotherapists in the treatment of back pain. It is characterised by a rapid high velocity, low amplitude thrust which commonly causes an audible 'pop' or 'cavitation' in the joint. Any beneficial effects are generally explained with reference to changes in vertebral joint movement. This paper looks at the process of spinal manipulation to see if there is reason to expect effects beyond simple changes in the biomechanics of the spine. It shows that during the process of spinal manipulation, rapid stretching of spinal muscles is inevitable. It goes on to review recent evidence that muscle stretch is a potent stimulus for the upregulation of a splice product of the insulin-like growth factor gene by the stretched muscle. Evidence that the product of this gene (mechano-growth factor; MGF) promotes muscle growth and repair (myotrophism) is presented, together with evidence that MGF promotes the growth and repair of neurones (neurotrophism). Against this background the hypothesis is proposed that one of the effects of spinal manipulation is to stretch spinal muscles which will upregulate MGF and result in local myotrophic and neurotrophic effects. This growth factor hypothesis represents a major departure from the biomechanical and biopsychosocial models currently used to explain the effects of spinal manipulation, and could provide the basis for further studies aimed at defining the molecular correlates of this type of manual therapy.