Intraesophageal manometry was performed on 14 healthy male volunteers divided into two groups. Group 1, composed of 4 subjects, received first phenylephrine (an alpha adrenergic stimulating drug) and then phentolamine (an alpha adrenergic blocking drug) intravenously. No effect on esophageal motility was observed following administration of either drug; however, adequate alpha stimulation or blockade of esophageal adrenergic receptors was probably not accomplished. Group 2 was composed of 10 subjects who received first isoproterenol (a beta stimulating drug) and then alprenolol (a beta blocking drug) intravenously. A significant decrease in resting pressure of the lower esophageal sphincter (LES) was observed in all of 9 subjects following isoproterenol. No effect was observed in the body of the esophagus. Following beta blockade with alprenolol, changes were observed in the body of the esophagus and in the LES. In the body of the esophagus, a rise in amplitude of contraction occurred in 9 of 10 subjects and prolongation of contraction was noted in 7 of 10 subjects. Changes in the LES were the most striking. Increase in amplitude of sphincteric contraction following deglutition was seen in 9 of 10 subjects. Prolongation of sphincteric contractions was most dramatic and was recognized in all 10 subjects. These data suggest an inhibitory beta receptor in the human distal esophagus. Stimulation of these receptors results in decreased LES resting pressure, while blockade of the receptors produces an increase in smooth muscle contraction—probably by removing inhibitory control.