Vasoactive intestinal polypeptide-containing nerves were examined in the lower esophagus of control and achalasia patients. The smooth muscle in patients with achalasia had conspicuously fewer vasoactive intestinal polypeptide-immunoreactive nerve fibers than specimens from control patients. Also the concentration of vasoactive intestinal polypeptide in the lower esophagus was much reduced in achalasia. In view of the potent smooth muscle relaxing effects of vasoactive intestinal polypeptide, it is suggested that the reduced number of vasoactive intestinal polypeptide fibers in the achalasic esophagus causes or at least contributes to the incomplete relaxation and the increased resting tone of the lower esophageal sphincter characteristic of this disease.