The parasympathetic nervous system primarily modulates visceral organs such as glands. Responses are never activated en masse as in the fight-or-flight sympathetic response. While providing important control of many tissues, the parasympathetic system, unlike the sympathetic system, is not crucial for the maintenance of life.

The parasympathetic nervous system is organized in a manner similar to the sympathetic nervous system. Its motor component consists of preganglionic and postganglionic neurons. The preganglionic neurons are located in specific cell groups (also called nuclei) in the brainstem or in the lateral horns of the spinal cord at sacral levels (segments S₂–S₄). (Because parasympathetic fibers exit from these two sites, the system is sometimes referred to as the craniosacral outflow.) Preganglionic axons emerging from the brainstem project to parasympathetic ganglia that are located in the head (ciliary, pterygopalatine [also called sphenopalatine], and otic ganglia) or near the heart (cardiac ganglia), embedded in the end organ itself (e.g., the trachea, bronchi, and gastrointestinal tract), or situated a short distance from the urinary bladder (pelvic ganglion). Both pre- and postganglionic neurons secrete acetylcholine as a neurotransmitter, but, like sympathetic ganglion cells, they also contain other neuroactive chemical agents that function as cotransmitters.

The third cranial nerve (oculomotor nerve) contains parasympathetic nerve fibers that regulate the iris and lens of the eye. From their origin in the Edinger-Westphal nucleus of the midbrain, preganglionic axons travel to the orbit and synapse on the ciliary ganglion. The ciliary ganglion contains two types of postganglionic neurons: one innervates smooth muscle of the iris and is responsible for pupillary constriction, and the other innervates ciliary muscle and controls the curvature of the lens.

Various secretory glands located in the head are under parasympathetic control. These include the lacrimal gland, which supplies tears to the cornea of the eye; salivary glands (sublingual, submandibular, and parotid glands), which produce saliva; and nasal mucous glands, which secrete mucus throughout the nasal air passages. The parasympathetic preganglionic neurons that regulate these functions originate in the reticular formation of the medulla oblongata. One group of parasympathetic preganglionic neurons belongs to the superior salivatory nucleus and lies in the rostral part of the medullary reticular formation. These neurons send axons out of the medulla in a separate branch of the seventh cranial nerve (facial nerve) called the intermediate nerve. Some of the axons innervate the pterygopalatine ganglion, and others project to the submandibular ganglion. Pterygopalatine ganglion cells innervate the vasculature of the brain and eye as well as the lacrimal gland, nasal glands, and palatine glands, while neurons of the submandibular ganglion innervate the submandibular and sublingual salivary glands. A second group of parasympathetic preganglionic neurons belongs to the inferior salivatory nucleus, located in the caudal part of the medullary reticular formation. Neurons of this group send axons out of the medulla in the ninth cranial (glossopharyngeal) nerve to the otic ganglion. From this site, postganglionic fibers travel to and innervate the parotid salivary gland.

Preganglionic parasympathetic fibers of the 10th cranial (vagus) nerve arise from two different sites in the medulla oblongata. Neurons that slow heart rate arise from a part of the ventral medulla called the nucleus ambiguus, while those that control functions of the gastrointestinal tract arise from the dorsal vagal nucleus. After exiting the medulla in the vagus nerve and traveling to their respective organs, the fibers synapse on ganglion cells embedded in the organs themselves. The vagus nerve also contains visceral afferent fibers that carry sensory information from organs of the neck (larynx, pharynx, and trachea), chest (heart and lungs), and gastrointestinal tract into a visceral sensory nucleus located in the medulla called the solitary tract nucleus.

Enteric nervous system

The enteric nervous system is composed of two plexuses, or networks of neurons, embedded in the wall of the gastrointestinal tract. The outermost plexus, located between the inner circular and outer longitudinal smooth-muscle layers of the gut, is called the Auerbach, or myenteric, plexus. Neurons of this plexus regulate peristaltic waves that move digestive products from the oral to the anal opening. In addition, myenteric neurons control local muscular contractions that are responsible for stationary mixing and churning. The innermost group of neurons is called the Meissner, or submucosal, plexus. This plexus regulates the configuration of the luminal surface, controls glandular secretions, alters electrolyte and water transport, and regulates local blood flow.

Three functional classes of intrinsic enteric neurons are recognized: sensory neurons, interneurons, and motor neurons. Sensory neurons, activated by either mechanical or chemical stimulation of the innermost surface of the gut, transmit information to interneurons located within the Auerbach and the Meissner plexi, and the interneurons relay the information to motor neurons. Motor neurons in turn modulate the activity of a variety of target cells, including mucous glands, smooth muscle cells, endocrine cells, epithelial cells, and blood vessels.

Extrinsic neural pathways also are involved in the control of gastrointestinal functions. Three types exist: intestinofugal, sensory, and motor. Intestinofugal neurons reside in the gut wall; their axons travel to the preaortic sympathetic ganglia and control reflex arcs that involve large portions of the gastrointestinal tract. Sensory neurons relay information regarding distention and acidity to the central nervous system. There are two types of sensory neurons: sympathetic neurons, which originate from dorsal-root ganglia found at the thoracic and lumbar levels; and parasympathetic neurons, which originate in the nodose ganglion of the vagus nerve or in dorsal-root ganglia at sacral levels S₂–S₄. The former innervate the gastrointestinal tract from the pharynx to the left colic flexure, and the latter innervate the distal colon and rectum. Each portion of the gastrointestinal tract receives a dual sensory innervation: pain sensations travel via sympathetic afferent fibers, and sensations that signal information regarding the chemical environment of the gut travel by way of parasympathetic fibers and are not consciously perceived.

The third extrinsic pathway, exercising motor control over the gut, arises from parasympathetic preganglionic neurons found in the dorsal vagal nucleus of the medulla oblongata and from sympathetic preganglionic neurons in the lateral horns of the spinal cord. These pathways provide modulatory commands to the intrinsic enteric motor system and are nonessential in that basic functions can be maintained in their absence.

Through the pathways described above, the parasympathetic system activates digestive processes while the sympathetic system inhibits them. The sympathetic system inhibits digestive processes by two mechanisms: (1) contraction of circular smooth muscle sphincters located in the distal portion of the stomach (pyloric sphincter), small intestine (ileo-cecal sphincter), and rectum (internal anal sphincter), which act as valves to prevent the oral-to-anal passage (as well as reverse passage) of digestive products; and (2) inhibition of motor neurons throughout the length of the gut. In contrast, the parasympathetic system provides messages only to myenteric motor neurons.