The esophagus is a region with three functional zones: (1) the upper esophageal sphincter; (2) the esophageal body; and (3) the lower esophageal sphincter. Control mechanisms within the central nervous system and peripherally serve to integrate these functional zones in a region where voluntary and involuntary control mechanisms and the activity of two different types of muscle are intimately coordinated. The distal 50 to 60 per cent of the esophagus in humans is entirely smooth muscle. Extrinsic control for esophageal motor function resides in a brainstem swallowing center with an afferent reception system, an efferent system of motor neurones, and a complex organizing or internuncial system of neurones. Sensory information from the esophagus is carried in the vagus nerves, but sensory pathways are also present in sympathetics entering the spinal cord. The vagus nerve receiving fibers both from the nucleus ambiguus and the dorsal motor nucleus innervates the striated and smooth muscle esophagus, respectively, including the sphincters. There is a myenteric nerve plexus in both the striated and smooth muscle segments. In the smooth muscle esophagus, there are two important effector neurones, an excitatory cholinergic neurone, and a nonadrenergic, noncholinergic (NANC) inhibitory neurone. The striated muscle contraction is directed and coordinated by sequential excitation through vagal fibers programmed by the central control mechanism. There are at least four potential control mechanisms for peristalsis in the smooth muscle esophagus: efferent motor fibers programmed by the swallowing center fire sequentially during peristalsis; the intramural neural mechanism can be excited to produce peristalsis near the onset of stimulation or with a delay after termination of stimulation; there is evidence for myogenic propagation of a peristaltic contraction. In humans, swallow-induced peristalsis is cholinergic and appears to result primarily from sequencing and activation of the intramural excitatory cholinergic neurones. Both central and peripheral levels of control are highly integrated to focus on the excitatory cholinergic neurones. It is likely that under normal circumstances, the central control mechanism exerts the dominant influence on these neurones for initiation and coordination of peristalsis in the smooth muscle esophagus. In humans, resting tone in the lower esophageal sphincter is predominantly cholinergic, but this tone is regulated by a balance between many excitatory and inhibitory influences. The relaxation on swallowing is caused by active inhibition of the muscle through NANC inhibitory neurones and cessation of tonic neural excitation to the