It is increasingly evident that gastrointestinal motility is subject to modulation by the immune system, and that the immunomodulation of motility is brought about by interactions of immune cells with nerves and muscle in the gut. The nature of these interactions is presently investigated in several in vitro and in vivo models. The existence of interactions between the immune and motor systems of the gut has clinical implications. Firstly, alterations of motility occur as part of the pathophysiology in inflammatory gastrointestinal diseases and likely account for some of the cardinal symptoms such as pain and diarrhea. Thus, a better understanding of the immunomodulation of motility may lead to a more specific symptomatic treatment. Secondly, immune activation may be involved in the pathogenesis of conditions that have hitherto been recognized as primary motility disorders. A deepened understanding of the pathogenesis of such conditions could bring about new strategies for their prevention and therapy.