The progress of gastrointestinal physiology is presently dominated by the concept of neuroendocrine regulation and the control of motility is in keeping with this concept. Progress in biochemistry, immunocytochemistry and radioimmunoassay in the past few years has produced a whole new collection of peptide molecules extracted from the digestive tract. Two facts are evident from these new data: (i) many peptides in the gastrointestinal tract are present in both endocrine cells and nerve fibers, and (ii) many peptides are found in both the brain and the gastrointestinal tract. There is thus a large wave of interest in the so-called brain-gut axis and in the relations between brain and gut and between nerves and hormones. The motile system of the gastrointestinal tract is a complex whole having several organizational levels. The morphological, fixed structure is a "cable" network comprising smooth muscle and intrinsic and extrinsic nerves. Control feedback loops may be evidenced at all levels-muscular, intrinsic, ganglionic and central. Local concentrations of circulating (endocrine) or paracrine peptides may act as modulators of this basic pattern by contributing to the depolarization or the hyperpolarization of smooth muscle cell membranes. The mode of action of these peptides reveals at least two different kinds of receptor sites: one on the smooth muscle cells and the other on the axons or cell bodies of intramural excitatory or inhibitory neurons. In addition, central nervous system effects may centrally modulate the long pathway reflexes travelling in the main vagosympathetic trunks. It is no longer possible to separate completely the neural from the hormonal in studying motility control. The whole neuroendocrine control complex must be investigated.