The main function of the smooth muscle of the gut is to mix and propel intralumenal contents, enabling efficient digestion of food, progressive absorption of nutrients, and eventual evacuation of residues. This function is regulated by the intrinsic electrical and mechanical properties of smooth muscle, such as the ability to maintain tone or undergo phasic contraction, and by alterations in these properties in response to hormonal and neural signals, particularly signals emanating from the enteric nervous system. The signal transduction pathways present in isolated circular and longitudinal muscle cells regulate tonic contraction and relaxation of intact, syncytial muscle. Extrinsic neurons of the sympathetic and parasympathetic systems influence smooth muscle indirectly by acting on neurons of the myenteric plexus. The disparate changes in signaling triggered by inflammatory cytokines and induced by nuclear factor‐kappa B in circular and longitudinal muscle disrupt the activity and functional coordination of the two muscle layers.