Stimulation of the esophagus activates the pharyngeal swallow response (EPSR) in human infants and animals. The aims of this study were to characterize the stimulus and response of the EPSR, and to determine the function and mechanisms generating the EPSR. Studies were conducted in 46 decerebrate cats in which pharyngeal, laryngeal and esophageal motility was monitored using EMG, strain gauges, or manometry. The esophagus was stimulated by balloon distension or luminal fluid infusion. We found that esophageal distension increased the chance of occurrence of the EPSR, but the delay was variable. The chance of occurrence of the EPSR was related to the position, magnitude, and length of the stimulus in the esophagus. The most effective stimulus was long, strong and situated in the cervical esophagus. Acidification of the esophagus activated pharyngeal swallows and sensitized the receptors which activate the EPSR. The EPSR was blocked by local anesthesia applied to the esophageal lumen and electrical stimulation of the RLNc activated the pharyngeal swallow response. We conclude that the EPSR is activated in a probabilistic manner. The receptors mediating the EPSR are probably mucosal slowly adapting tension receptors. The sensory neural pathway includes the RLNc and SLN. We hypothesize that since the EPSR is observed in human infants and animals, but not human adults, activation of EPSR is related to the elevated position of the larynx. In this situation, the EPSR occurs rather than secondary peristalsis, to prevent supra-esophago reflux when the esophageal bolus is in the proximal esophagus.